Showing papers in "Hypertension in 2001"

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.

Abstract: Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.

Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.

Abstract: To test the predictive values of and independent contributions to cardiovascular and all-cause mortality of various arterial parameters exploring characteristics of the arterial wall at different s...

Elevated Uric Acid Increases Blood Pressure in the Rat by a Novel Crystal-Independent Mechanism

Abstract: An elevation in circulating serum uric acid is strongly associated with the development of hypertension and renal disease, but whether uric acid has a causal role or whether it simply indicates patients at risk for these complications remains controversial. We tested the hypothesis that uric acid may have a causal role in the development of hypertension and renal disease by examining the effects of mild hyperuricemia in rats. Mild hyperuricemia was induced in rats by providing a uricase inhibitor (oxonic acid) in the diet. Hyperuricemic rats developed elevated blood pressure after 3 weeks, whereas control rats remained normotensive. The development of hypertension was prevented by concurrent treatment with either a xanthine oxidase inhibitor (allopurinol) or a uricosuric agent (benziodarone), both of which lowered uric acid levels. Blood pressure could also be lowered by reducing uric acid levels with either allopurinol or oxonic acid withdrawal. A direct relationship was found between blood pressure and uric acid (r=0.75, n=69), with a 10-mm Hg blood pressure increase for each 0.03-mmol/L (0.5-mg/dL) incremental rise in serum uric acid. The kidneys were devoid of urate crystals and were normal by light microscopy. However, immunohistochemical stains documented an ischemic type of injury with collagen deposition, macrophage infiltration, and an increase in tubular expression of osteopontin. Hyperuricemic rats also exhibited an increase in juxtaglomerular renin and a decrease in macula densa neuronal NO synthase. Both the renal injury and hypertension were reduced by treatment with enalapril or L-arginine. In conclusion, mild hyperuricemia causes hypertension and renal injury in the rat via a crystal-independent mechanism, with stimulation of the renin-angiotensin system and inhibition of neuronal NO synthase.

Diabetes, Hypertension, and Cardiovascular Disease: An Update

Abstract: Cardiovascular diseases (CVDs) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. Hypertension is approximately twice as frequent in patients with diabetes compared with patients without the disease. Conversely, recent data suggest that hypertensive persons are more predisposed to the development of diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons with coexistent diabetes and hypertension. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and "diabetic cardiomyopathy." The cardiomyopathy associated with diabetes is a unique myopathic state that appears to be independent of macrovascular/microvascular disease and contributes significantly to CVD morbidity and mortality in diabetic patients, especially those with coexistent hypertension. This update reviews the current knowledge regarding these risk factors and their treatment, with special emphasis on the cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic cardiomyopathy. This update also examines the role of the renin-angiotensin system in the increased risk for CVD in diabetic patients and the impact of interrupting this system on the development of clinical diabetes as well as CVD.

Prospective Evaluation of a Method for Estimating Ascending Aortic Pressure From the Radial Artery Pressure Waveform

Abstract: Pressure wave reflection in the upper limb causes amplification of the arterial pulse so that radial systolic and pulse pressures are greater than in the ascending aorta. Wave transmission properti...

Gender Differences in the Regulation of Blood Pressure

Abstract: Men are at greater risk for cardiovascular and renal disease than are age-matched, premenopausal women. Recent studies using the technique of 24-hour ambulatory blood pressure monitoring have shown that blood pressure is higher in men than in women at similar ages. After menopause, however, blood pressure increases in women to levels even higher than in men. Hormone replacement therapy in most cases does not significantly reduce blood pressure in postmenopausal women, suggesting that the loss of estrogens may not be the only component involved in the higher blood pressure in women after menopause. In contrast, androgens may decrease only slightly, if at all, in postmenopausal women. In this review the possible mechanisms by which androgens may increase blood pressure are discussed. Findings in animal studies show that there is a blunting of the pressure-natriuresis relationship in male spontaneously hypertensive rats and in ovariectomized female spontaneously hypertensive rats treated chronically with testosterone. The key factor in controlling the pressure-natriuresis relationship is the renin-angiotensin system (RAS). The possibility that androgens increase blood pressure via the RAS is explored, and the possibility that the RAS also promotes oxidative stress leading to production of vasoconstrictor substances and reduction in nitric oxide availability is proposed.

Vascular Remodeling in Hypertension Roles of Apoptosis, Inflammation, and Fibrosis

Abstract: Remodeling of large and small arteries contributes to the development and complications of hypertension. The focus of this review is some of the mechanisms involved in the remodeling of small arteries in hypertension. In hypertension, changes in small artery structure are basically of 2 kinds: (1) inward eutrophic remodeling, in which outer and lumen diameters are decreased, media/lumen ratio is increased, and cross-sectional area of the media is unaltered; and (2) hypertrophic remodeling, in which the media thickens to encroach on the lumen, resulting in increased media cross-sectional area and media/lumen ratio. Growth, apoptosis, inflammation, and fibrosis contribute to vascular remodeling in hypertension. Apoptosis is gene-regulated cell death, with minimal membrane disruption and inflammation, that counters cell proliferation and fine-tunes developmental growth. Apoptosis has been reported in hypertension to be both increased and decreased in different tissues, including blood vessels. Inflammation, which may be low grade, probably plays an important role in triggering fibrosis in cardiovascular disease and hypertension. Vascular fibrosis entails accumulation of collagen, fibronectin, and other extracellular matrix components in the vessel wall and is an important aspect of extracellular matrix remodeling in hypertension. Associated with this, there may be increases in cell-matrix attachment sites (integrins) and changes in their topographical localization that may modulate arterial structure. Imbalance in matrix metalloproteinase/tissue inhibitors of metalloproteinases may contribute to alteration in collagen turnover and extracellular matrix remodeling. Chronic vasoconstriction may lead to embedding of the contracted vessel structure in a remodeled extracellular matrix, contributing to the inward remodeling of the blood vessel as smooth muscle cells are rearranged around a smaller lumen. The resulting remodeling of small arteries may initially be adaptive, but eventually it becomes maladaptive and compromises organ function, contributing to cardiovascular complications of hypertension.

Arterial Wave Reflections and Survival in End-Stage Renal Failure

Abstract: The increased effect of arterial wave reflections on central arteries like the common carotid artery seen in end-stage renal failure (ESRF) patients favors myocardial hypertrophy and oxygen consumption and alters coronary blood flow distribution. Nevertheless, the impact of wave reflection on the outcome and end points such as mortality remains to be demonstrated. One hundred eighty ESRF patients (age, 54±16 years) were monitored for 52±36 months (mean±SD). Seventy deaths, including 40 cardiovascular (CV) and 30 non-CV events, occurred. At entry, patients, in addition to standard clinical and biochemical analyses, underwent aortic pulse wave velocity measurement and determination of arterial wave reflexion by applanation tonometry on the common carotid artery that was expressed as augmentation index. Cox analyses demonstrated that predictors of all-cause and CV mortality were age, aortic pulse wave velocity, low diastolic blood pressure, preexisting CV disease, and increased augmentation index, whereas the prescription of an ACE inhibitor had a favorable effect on survival. After adjustment for all confounding factors, the risk ratio for each 10% increase in augmentation index was 1.51 (95% confidence interval, 1.23 to 1.86; P P

Effects of Alcohol Reduction on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials

Abstract: Alcohol drinking has been associated with increased blood pressure in epidemiological studies. We conducted a meta-analysis of randomized controlled trials to assess the effects of alcohol reductio...

Tissue Angiotensin and Pathobiology of Vascular Disease A Unifying Hypothesis

Abstract: —There is increasing evidence that direct pathobiological events in the vessel wall play an important role in vascular disease. An important mechanism involves the perturbation of the homeostatic balance between NO and reactive oxygen species. Increased reactive oxygen species can inactivate NO and produce peroxynitrite. Angiotensin II is a potent mediator of oxidative stress and stimulates the release of cytokines and the expression of leukocyte adhesion molecules that mediate vessel wall inflammation. Inflammatory cells release enzymes (including ACE) that generate angiotensin II. Thus, a local positive-feedback mechanism could be established in the vessel wall for oxidative stress, inflammation, and endothelial dysfunction. Angiotensin II also acts as a direct growth factor for vascular smooth muscle cells and can stimulate the local production of metalloproteinases and plasminogen activator inhibitor. Taken together, angiotensin II can promote vasoconstriction, inflammation, thrombosis, and vascular remodeling. In this article, we propose a model that unifies the interrelationship among cardiovascular risk factors, angiotensin II, and the pathobiological mechanisms contributing to cardiovascular disease. This model may also explain the beneficial effects of ACE inhibitors on cardiovascular events beyond blood pressure reduction.

Stroke Prognosis and Abnormal Nocturnal Blood Pressure Falls in Older Hypertensives

Abstract: It remains uncertain whether abnormal dipping patterns of nocturnal blood pressure influence the prognosis for stroke. We studied stroke events in 575 older Japanese patients with sustained hypertension determined by ambulatory blood pressure monitoring (without medication). They were subclassified by their nocturnal systolic blood pressure fall (97 extreme-dippers, with >/=20% nocturnal systolic blood pressure fall; 230 dippers, with >/=10% but /=0% but <10% fall; and 63 reverse-dippers, with <0% fall) and were followed prospectively for an average duration of 41 months. Baseline brain magnetic resonance imaging (MRI) disclosed that the percentages with multiple silent cerebral infarct were 53% in extreme-dippers, 29% in dippers, 41% in nondippers, and 49% in reverse-dippers. There was a J-shaped relationship between dipping status and stroke incidence (extreme-dippers, 12%; dippers, 6.1%; nondippers, 7.6%; and reverse-dippers, 22%), and this remained significant in a Cox regression analysis after controlling for age, gender, body mass index, 24-hour systolic blood pressure, and antihypertensive medication. Intracranial hemorrhage was more common in reverse-dippers (29% of strokes) than in other subgroups (7.7% of strokes, P=0.04). In the extreme-dipper group, 27% of strokes were ischemic strokes that occurred during sleep (versus 8.6% of strokes in the other 3 subgroups, P=0.11). In conclusion, in older Japanese hypertensive patients, extreme dipping of nocturnal blood pressure may be related to silent and clinical cerebral ischemia through hypoperfusion during sleep or an exaggerated morning rise of blood pressure, whereas reverse dipping may pose a risk for intracranial hemorrhage.

Predominance of Isolated Systolic Hypertension Among Middle-Aged and Elderly US Hypertensives: Analysis Based on National Health and Nutrition Examination Survey (NHANES) III

Abstract: The purpose of the present study was to examine patterns of systolic and diastolic hypertension by age in the nationally representative National Health and Nutrition Examination Survey (NHANES) III...

Blood Pressure and Inflammation in Apparently Healthy Men

Abstract: Inflammation plays an important role in the development of atherosclerosis, but the specific stimuli governing cytokine release in atherogenesis are unknown. We examined the hypothesis that hypertension may increase the risk of atherosclerosis via proinflammatory effects. In a cross-sectional study involving 508 apparently healthy men, we studied the association between blood pressure and baseline plasma concentrations of 2 inflammatory markers, intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6). Increase in systolic blood pressure (SBP) (P=0.003), pulse pressure (PP) (P=0.019), and mean arterial pressure (P=0.014) was significantly associated with levels of sICAM-1. All of these measures of blood pressure, as well as diastolic blood pressure (DBP), were significantly associated with levels of IL-6 (all, P

Age-Related Reduction of NO Availability and Oxidative Stress in Humans

Abstract: Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P 60 years). In young hypertensive patients (age 30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.

Telomere Length as an Indicator of Biological Aging: The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity

Abstract: Chronological age is the primary determinant of stiffness of central arteries. Increased stiffness is an independent indicator of cardiovascular risk. The aim of this study was to determine whether...

Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction.

Abstract: Studies over the past decade have provided a better understanding of the potential mechanisms responsible for the pathogenesis of preeclampsia. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion as a result of abnormal cytotrophoblast invasion of spiral arterioles. Placental ischemia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin and thromboxane, increased vascular sensitivity to angiotensin II, and decreased formation of vasodilators such as NO and prostacyclin. These endothelial abnormalities, in turn, cause hypertension by impairing renal-pressure natriuresis and increasing total peripheral resistance. The quantitative importance of the various endothelial and humoral factors in mediating the reduction in renal hemodynamic and excretory function and elevation in arterial pressure during preeclampsia are still unclear. Results from ongoing basic and clinical studies, however, should provide new and important information regarding the physiological mechanisms responsible for the elevation in arterial pressure in women with preeclampsia.

Salt Sensitivity, Pulse Pressure, and Death in Normal and Hypertensive Humans

Abstract: Although factors such as age, blood pressure, and its responsiveness to changes in sodium balance and extracellular fluid volume status (salt sensitivity) are associated with an increased risk of end-organ disease and cardiovascular events in hypertensive subjects, no such relationship with mortality has been demonstrated for salt sensitivity in normotensive subjects. We conducted long-term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago. We ascertained the status of 596 subjects (85% of the total population), 123 (21%) of whom had died. The following initial measurements were significantly (P 25 years when initially studied were found to have a cumulative mortality similar to that of hypertensive subjects, whereas salt-resistant normotensive subjects had increased survival ( P

Angiotensin II and Renal Fibrosis

Abstract: Angiotensin (Ang) II, the main peptide of the renin angiotensin system (RAS), is a renal growth factor, inducing hyperplasia/hypertrophy depending on the cell type. This vasoactive peptide activates mesangial and tubular cells and interstitial fibroblasts, increasing the expression and synthesis of extracellular matrix proteins. Some of these effects seem to be mediated by the release of other growth factors, such as TGF-beta. In experimental models of kidney damage, renal RAS activation, cell proliferation, and upregulation of growth factors and matrix production were described. In some of these models, blockade of Ang II actions by ACE inhibitors and angiotensin type 1 (AT(1)) antagonists prevents proteinuria, gene expression upregulation, and fibrosis, as well as inflammatory cell infiltration. Interestingly, Ang II could also be involved in the fibrotic process because of its behavior as a proinflammatory cytokine, participating in various steps of the inflammatory response: Ang II (1) activates mononuclear cells and (2) increases proinflammatory mediators (cytokines, chemokines, adhesion molecules, nuclear factor kappaB). Finally, Ang II also regulates matrix degradation. These data show that drugs controlling this complex vasoactive peptide are probably one of the best ways of avoiding fibrosis in progressive renal diseases.

Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.

Abstract: In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.

Superoxide Excess in Hypertension and Aging A Common Cause of Endothelial Dysfunction

Abstract: There is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O 2 − ) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O 2 − , and age in normotensive Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O 2 − generation by aortic rings was measured before and after removal of the endothelium or incubation with N G nitro-l-arginine methyl ester, diphenyleneiodonium, or apocynin. Levels of p22phox were studied with immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO bioavailability was significantly lower in old WKY compared with young WKY ( P =0.0009) and in old SHRSP compared with young SHRSP ( P =0.005). O 2 − generation was significantly greater in old WKY compared with young WKY ( P =0.0001). Removal of the endothelium and N G nitro-l-arginine methyl ester treatment resulted in a significant reduction in O 2 − generation in old SHRSP ( P =0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O 2 − generation in 12-month WKY ( P =0.008) and 12-month SHRSP ( P =0.009). Apocynin attenuated O 2 − generation by older WKY ( P =0.038) and SHRSP ( P =0.028). p22phox was increased in older animals compared with young. We conclude that NO bioavailability decreases with age in female WKY and SHRSP. O 2 − generation increases with age in WKY and is higher in SHRSP and may contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the age-related increase in O 2 − .

Improvement in Blood Pressure, Arterial Stiffness and Wave Reflections With a Very-Low-Dose Perindopril/Indapamide Combination in Hypertensive Patient: A Comparison With Atenolol

Abstract: International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.

HMG-CoA Reductase Inhibitors Improve Endothelial Dysfunction in Normocholesterolemic Hypertension via Reduced Production of Reactive Oxygen Species

Abstract: —3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce cardiovascular mortality associated with hypercholesterolemia. There is evidence that statins exert beneficial effects in part through direct effects on vascular cells independent of lowering plasma cholesterol. We characterized the effect of a 30-day treatment with atorvastatin in normocholesterolemic, spontaneously hypertensive rats (SHR). Systolic blood pressure was significantly decreased in atorvastatin-treated rats (184±5 versus 204±6 mm Hg for control). Statin therapy improved endothelial dysfunction, as assessed by carbachol-induced vasorelaxation in aortic segments, and profoundly reduced angiotensin II–induced vasoconstriction. Angiotensin type 1 (AT 1 ) receptor, endothelial cell NO synthase (ecNOS), and p22phox mRNA expression were determined with quantitative reverse transcription–polymerase chain reaction. Atorvastatin treatment downregulated aortic AT 1 receptor mRNA expression to 44±12% of control and reduced mRNA expression of the essential NAD(P)H oxidase subunit p22phox to 63±7% of control. Aortic AT 1 receptor protein expression was consistently decreased. Vascular production of reactive oxygen species was reduced to 62±12% of control in statin-treated SHR, as measured with lucigenin chemiluminescence assays. Accordingly, treatment of SHR with the AT 1 receptor antagonist fonsartan improved endothelial dysfunction and reduced vascular free-radical release. Moreover, atorvastatin caused an upregulation of ecNOS mRNA expression (138±7% of control) and an enhanced ecNOS activity in the vessel wall (209±46% of control). Treatment of SHR with atorvastatin causes a significant reduction of systolic blood pressure and a profound improvement of endothelial dysfunction mediated by a reduction of free radical release in the vasculature. The underlying mechanism could in part be based on the statin-induced downregulation of AT 1 receptor expression and decreased expression of the NAD(P)H oxidase subunit p22phox, because AT 1 receptor activation plays a pivotal role for the induction of this redox system in the vessel wall.

Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase

Abstract: Increased vascular reactive oxygen species production, especially superoxide anion, contributes significantly in the functional and structural alterations present in hypertension. An enhanced superoxide production causes a diminished NO bioavailability by an oxidative reaction that inactivates NO. Exaggerated superoxide levels and a low NO bioavailability lead to endothelial dysfunction and hypertrophy of vascular cells. It has been shown that the enzyme NAD(P)H oxidase plays a major role as the most important source of superoxide anion in vascular cells. Several experimental observations have shown an enhanced superoxide generation as a result of the activation of vascular NAD(P)H oxidase in hypertension. Although this enzyme responds to stimuli such as vasoactive factors, growth factors, and cytokines, some recent data suggest the existence of a genetic background modulating the expression of its different components. New polymorphisms have been identified in the promoter of the p22 phox gene, an essential subunit of NAD(P)H oxidase, influencing the activity of this enzyme. Genetic investigations of these polymorphisms will provide novel markers for determination of genetic susceptibility to oxidative stress in hypertension.

Diabetes, Hypertension, and Cardiovascular Disease: An Update

Abstract: To the Editor: Sowers et al are to be commended for writing a thorough review on the diabetic hypertensive patient.1 In doing so, they came to the conclusion that, “Results of the SHEP) [2] and the UKPDS) [3] trials suggest that diuretics and β-blockers as well as ACE inhibitors are also useful therapeutic agents in diabetic hypertensive patients who often require ≥2 drugs to control blood pressure adequately. [4]”) Although we agree with this statement, it should be pointed out that β-blockers seem to be far less efficacious than the other drug classes in this …

Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR

Abstract: Ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) have antioxidant properties that could improve redox-sensitive vascular changes associated with hypertension. We determined whether vitamins C and E influence vascular function and structure in hypertension by modulating activity of NADPH oxidase and superoxide dismutase (SOD). Adult stroke-prone spontaneously hypertensive rats (SHRSP) were divided into 3 groups: control (C; n=6), vitamin C-treated (vit C, 1000 mg/day; n=7), and vitamin E-treated (vit E, 1000 IU/day; n=8). All rats were fed 4% NaCl. Blood pressure was measured weekly. After 6 weeks of treatment, the rats were killed, and mesenteric arteries were mounted as pressurized preparations. Vascular O(2)(-) generation and NADPH oxidase activity were measured by chemiluminescence. Vascular SOD activity and plasma total antioxidant status (TAS) were determined spectrophotometrically. Blood pressure increased from 212+/-7 to 265+/-6 mm Hg in controls. Treatment prevented progression of hypertension (vit C, 222+/-6 to 234+/-14 mm Hg; vit E, 220+/-9 to 227+/-10 mm Hg). Acetylcholine-induced vasodilation was improved (P<0.05), and media-to-lumen ratio was reduced (P<0.05) in the treated rats. O(2)(-) was lower in vitamin-treated groups compared with controls (vit C, 10+/-4 nmol. min(-1). g(-1) dry tissue weight; vit E, 9.6+/-3.5 nmol. min(-1). g(-1) dry tissue weight; C, 21+/-9 nmol. min(-1). g(-1) dry tissue weight; P<0.05). Both vitamin-treated groups showed significant improvement (P<0.01) in TAS. These effects were associated with decreased activation of vascular NADPH oxidase (vit C, 46+/-10; vit E, 50+/-9; C, 70+/-16 nmol. min(-1). g(-1) dry tissue weight, P<0.05) and increased activation of SOD (vit C, 12+/-2; vit E, 8+/-1; C, 4.6+/-1 U/mg; P<0.05). Our results demonstrate that vitamins C and E reduce oxidative stress, improve vascular function and structure, and prevent progression of hypertension in SHRSP. These effects may be mediated via modulation of enzyme systems that generate free radicals.

Vasoactive Drugs Influence Aortic Augmentation Index Independently of Pulse-Wave Velocity in Healthy Men

Abstract: Aortic augmentation index, a measure of central systolic blood pressure augmentation arising mainly from pressure-wave reflection, increases with vascular aging. The augmentation index is influenced by aortic pulse-wave velocity (related to aortic stiffness) and by the site and extent of wave reflection. To clarify the relative influence of pulse-wave velocity and wave reflection on the augmentation index, we studied the association between augmentation index, pulse-wave velocity, and age and examined the effects of vasoactive drugs to determine whether altering vascular tone has differential effects on pulse-wave velocity and the augmentation index. We made simultaneous measurements of the augmentation index and carotid-to-femoral pulse-wave velocity in 50 asymptomatic men aged 19 to 74 years at baseline and, in a subset, during the administration of nitroglycerin, angiotensin II, and saline vehicle. The aortic augmentation index was obtained by radial tonometry (Sphygmocor device, PWV Medical) with the use of an inbuilt radial to aortic transfer function. In multiple regression analysis, the aortic augmentation index was independently correlated only with age (R=0.58, P<0.0001). Nitroglycerin (3 to 300 microg/min IV) reduced the aortic augmentation index from 4.8+/-2.3% to -11.9+/-5.3% (n=10, P<0.002). Angiotensin II (75 to 300 ng/min IV) increased the aortic augmentation index from 9.3+/-2.4% to 18.3+/-2.9% (n=12, P<0.001). These drugs had small effects on aortic pulse-wave velocity, producing mean changes from baseline of <1 m/s (each P<0.05). In healthy men, vasoactive drugs may change aortic augmentation index independently from aortic pulse-wave velocity.

Aortic Stiffness Is Associated With Visceral Adiposity in Older Adults Enrolled in the Study of Health, Aging, and Body Composition

Abstract: The central arteries stiffen with age, causing hemodynamic alterations that have been associated with cardiovascular events. Changes in body fat with age may be related to aortic stiffening. The association between vascular stiffness and body fat was evaluated in 2488 older adults (mean age, 74 years; 52% female; 40% black) enrolled in the Study of Health, Aging, and Body Composition (Health ABC), a prospective study of changes in weight and body composition. Clinical sites were located in Pittsburgh, Pa, and Memphis, Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness. A faster pulse wave velocity indicates a stiffer aorta. Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography. Independent of age and blood pressure, pulse wave velocity was positively associated with weight, abdominal circumference, abdominal subcutaneous fat, abdominal visceral fat, thigh fat area, and total fat (P<0.001 for all). The strongest association was with abdominal visceral fat. Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose, insulin, and hemoglobin A1c (P<0.001 for all). In multivariate analysis, independent positive associations with pulse wave velocity were found for age, systolic blood pressure, heart rate, abdominal visceral fat, smoking, hemoglobin A1c, and history of hypertension. The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight. Among older adults, higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity.

Endothelium-Derived Nitric Oxide Regulates Arterial Elasticity in Human Arteries In Vivo

Abstract: Arterial elasticity is determined by structural characteristics of the artery wall and by vascular smooth muscle tone. The identity of endogenous vasoactive substances that regulate elasticity has not been defined in humans. We hypothesized that NO, a vasodilator released constitutively by the endothelium, augments arterial elasticity. Seven healthy young men were studied. A 20-MHz intravascular ultrasound catheter was introduced through an arterial sheath to measure brachial artery cross-sectional area, wall thickness, and intra-arterial pressure. After control was established, indices of elasticity (pressure-area relationship, instantaneous compliance, and stress-strain, pressure-incremental elastic modulus (Einc), and pressure-pulse wave velocity relationships) were examined over 0 to 100 mm Hg transmural pressure obtained by inflation of an external cuff. Thereafter, the basal production of endothelium-derived NO was inhibited by N G -monomethyl-L-arginine (L-NMMA) (4 and 8 mg/min). Finally, nitroglycerin (2.5 and 12.5 g/min), an exogenous donor of NO, was given to relax the vascular smooth muscle. Elasticity was measured under all of these conditions. L-NMMA (8 mg/min) decreased brachial artery area (P0.016) and compliance (P0.0001) and increased Einc (P0.01) and pulse wave velocity (P0.0001). Nitroglycerin (12.5 g/min) increased brachial artery area (P0.001) and compliance (P0.001) and decreased pulse wave velocity (P0.02). NO, an endothelium-derived vasodilator, augments arterial elasticity in the human brachial artery. Loss of constitutively released NO associated with cardiovascular risk factors may adversely affect arterial elasticity in humans. (Hypertension. 2001;38:1049-1053.)

Alcohol Consumption and the Incidence of Hypertension: The Atherosclerosis Risk in Communities Study

Abstract: A close relationship between alcohol consumption and hypertension has been established, but it is unclear whether there is a threshold level for this association. In addition, it has infrequently been studied in longitudinal studies and in black people. In a cohort study, 8334 of the Atherosclerosis Risk in Communities (ARIC) Study participants, aged 45 to 64 years at baseline, who were free of hypertension and coronary heart disease had their blood pressures ascertained after 6 years of follow-up. Alcohol consumption was assessed by dietary interview. The type of alcoholic beverage predominantly consumed was defined by the source of the largest amount of ethanol consumed. Incident hypertension was defined as a systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg or use of antihypertensive medication. There was an increased risk of hypertension in those who consumed large amounts of ethanol (>/=210 g per week) compared with those who did not consume alcohol over the 6 years of follow-up. The adjusted odds ratios (95% confidence interval) were 1.2 (0.85 to 1.67) for white men, 2.02 (1.08 to 3.79) for white women, and 2.31 (1.11 to 4.86) for black men. Only 4 black women reported drinking >210 g ethanol per week. At low to moderate levels of alcohol consumption (1 to 209 g per week), the adjusted odds ratios (95% confidence interval) were 0.88 (0.71 to 1.08) in white men, 0.89 (0.73 to 1.09) in white women, 1.71 (1.11 to 2.64) in black men, and 0.88 (0.59 to 1.33) in black women. Systolic and diastolic blood pressures were higher in black men who consumed low to moderate amounts of alcohol compared with the nonconsumers but not in the 3 other race-gender strata. Models with polynomial terms of alcohol exposure suggested a nonlinear association in white and black men. Higher levels of consumption of all types of alcoholic beverages were associated with a higher risk of hypertension for all race-gender strata. The consumption of alcohol in amounts >/=210 g per week is an independent risk factor for hypertension in free-living North American populations. The consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.

Association Between Smoking and Blood Pressure: Evidence From the Health Survey for England

Abstract: Cigarette smoking causes acute blood pressure (BP) elevation, although some studies have found similar or lower BPs in smokers compared with nonsmokers. Cross-sectional data from 3 years (1994 to 1996) of the annual Health Survey for England were used to investigate any difference in BP between smokers and nonsmokers in a nationally representative sample of adults (>/=16 years old). Randomly selected adults (33 860; 47% men) with valid body mass index (BMI) and BP measurements provided data on smoking status (never, past, or current) and were stratified into younger (16 to 44 years old) and older (>/=45 years old) age groups. Analyses provided between 89% and 94% power to detect a difference of 2 mm Hg systolic BP between smokers and nonsmokers in the 4 age/gender strata (alpha=0.05). Older male smokers had higher systolic BP adjusted for age, BMI, social class, and alcohol intake than did nonsmoking men. No such differences were seen among younger men or for diastolic blood pressure in either age group. Among women, light smokers (1 to 9 cigarettes/d) tended to have lower BPs than heavier smokers and never smokers, significantly so for diastolic BP. Among men, a significant interaction between BMI and the BP-smoking association was observed. In women, BP differences between nonsmokers and light smokers were most marked in those who did not drink alcohol. These data show that any independent chronic effect of smoking on BP is small. Differences between men and women in this association are likely to be due to complex interrelations among smoking, alcohol intake, and BMI.