Showing papers by "Roland E. Schmieder published in 1998"

Update on reversal of left ventricular hypertrophy in essential hypertension (a meta-analysis of all randomized double-blind studies until December 1996).

Abstract: Objective. To provide an update on the ability of different antihypertensive drugs to reduce left ventricular hypertrophy in essential hypertension. Data sources. Relevant medical databases including MEDLINE, BIOSIS PREVIEWS, EMBASE, and SCISEARCH as well as review articles to December 1996. Study selection. Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. Data extraction. Literature search and data extraction according to a prefixed scheme performed independently by two investigators. The primary parameter was reduction of left ventricular mass by antihypertensive therapy with placebo, diuretics, β-blockers, calcium channel blockers, or ACE-inhibitors. Data synthesis. Fifty studies published till the end of December 1996 were identified. They comprised a total of 1715 patients in 13 placebo (n=165, age: 50±3 years) and 89 active treatment arms (n=1550, age: 56±10 years) respectively. Overall, for active treatment left ventricular mass index was the more reduced the greater the decrease in systolic blood pressure, (r= 0.27; P<0.05), the longer the duration of therapy (r=0.36; P<0.001), and the higher the pretreatment value of left ventricular mass index (r= 0.53; P<0.001). Left ventricular mass index was decreased by 12% with ACE-inhibitors (95%) CI: 9.0-14.5%), by 11% with calcium channel blockers (95%) CI: 7.8-13.7%), by 5%) with β-blockers (95%) CI: 1.2-7.3%) and by 8% with diuretics (95%) CI: 3.9-11.1%) (overall P<0.01). Subsequent tests revealed that ACE-inhibitors and calcium channel blockers were more effective than β-blockers in reducing left ventricular mass index (P<0.05). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<0.05). Conclusions. Decrease in systolic blood pressure, duration of antihypertensive therapy, degree of pretreatment left ventricular hypertrophy and antihypertensive drug class determined the reduction of left ventricular hypertrophy. ACE-inhibitors and calcium channel blockers were more potent in reducing left ventricular mass than β-blockers, with diuretics in the intermediate range.

Effects of naloxone on hemodynamic and sympathetic nerve responses to pain in normotensive vs. borderline hypertensive men.

Abstract: Pain sensitivity decreases with increasing resting blood pressure. This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26 +/- 2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3 +/- 1 vs. 1 +/- 1 bpm; P < 0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5 +/- 1 to 9 +/- 1 bursts/min, and, from 100 +/- 23 to 204 +/- 36 units/min, respectively; P < 0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects (P < 0.005). Naloxone increased pain rating in the NT group (from 194 +/- 9 to 218 +/- 13; P < 0.005) but not in the borderline hypertensive group (160 +/- 8 vs. 168 +/- 10; P = 0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.

Impact of dietary sodium intake on left ventricular diastolic filling in early essential hypertension.

Abstract: Aims Dietary sodium intake modulates left ventricular hypertrophy in established essential hypertension independent of blood pressure level. We conducted this study to elucidate the relationship between sodium intake and left ventricular structural or functional changes in early essential hypertension. Methods Forty-four young male patients (age 25.9 ± 2.6 years) with mild essential hypertension that had never been treated and 45 normotensive male control subjects of similar age were examined. Dietary sodium intake was measured from 24 h urinary sodium excretion, blood pressure from 24 h ambulatory monitoring (SpaceLabs 90207), left ventricular structure from 2-D guided M-mode echocardiography, and diastolic filling of the left ventricle (as the main compound of diastolic function in a young population) by pulse-wave Doppler sonography. Results In hypertensive patients, daily sodium excretion correlated with the ratio of late (A) to early (E) maximum velocity (Vmax AlE; r= +0.27, P =0.07), velocity time integrals (AlE; r= +0.54, P<0.001) as well as atrial contribution, as a percent of left ventricular filling (VH A TCO; r= +0.52, P<0.001) independent of heart rate, whereas the opposite correlations were observed in normotensives (all P<0·001). Stepwise multiple regression analysis confirmed these results. Sodium excretion emerged as the strongest independent determinant of impaired diastolic filling in hypertensive patients (velocity time integrals AlE: R2 =0.49, β= +0.57, P =0.0001; VH ATCO: R2 = 0.48, β= +0.56, P<0.0001; Vmax AlE: ns). In normotensive subjects, sodium excretion was a similar strong, but inverse determinant of diastolic filling (velocity time integrals AlE: R2 =0.40, β= −0.43, P =0.0028). Heart rate was a strong determinant of diastolic filling in hypertensive patients (β= +0.55, P =0.0002) and in normotensive subjects (β= +0.34, P =0·011). Left ventricular mass and enddiastolic volume index were not related to diastolic filling in either group. Conclusion In early essential hypertension, sodium excretion is correlated with impaired left ventricular diastolic filling independent of left ventricular mass. The reninangiotensin-aldosterone system might be a mediator of the observed correlation.

Inadequate suppression of angiotensin II modulates left ventricular structure in humans.

Abstract: BACKGROUND In a previous study we found that high angiotensin II levels in relation to the corresponding urinary sodium excretion aggravate left ventricular hypertrophy in hypertensive patients. To analyze whether a dysregulation of the renin angiotensin aldosterone system determines left ventricular structure in young individuals, we examined whether the response of angiotensin II after increasing salt intake is related to left ventricular structure. METHODS In 51 young, male Caucasians with normal or mildly elevated blood pressure, left ventricular structure, 24-hour ambulatory blood pressure and dietary sodium intake (as estimated by 24-hour sodium excretion) were determined in parallel with plasma renin activity, angiotensin II, and aldosterone concentrations. Angiotensin II concentration and 24-hour sodium excretion were measured twice: firstly on a normal Bavarian diet and secondly at high salt intake to determine the resulting suppression of the renin-angiotensin-aldosterone system. RESULTS Body mass index (r = 0.42, p < 0.001) and both systolic (r = 0.28, p < 0.05) and diastolic (r = 0.25, p < 0.05) 24-hour ambulatory blood pressure correlated with left ventricular mass. No direct relationship was found between left ventricular structure and baseline angiotensin II concentration. The lower the physiological decrease of angiotensin II after high oral salt intake, i.e. the higher the angiotensin II level after salt intake remained, the greater was left ventricular mass (r = 0.38; p < 0.006) even after taking 24-hour ambulatory blood pressure into account (partial correlation; r = 0.43, p < 0.005). Consistently, angiotensin II concentration at high salt intake correlated with left ventricular mass independently of ambulatory blood pressure (partial correlation: r = 0.29, p < 0.05). Subgroup analysis revealed that the increase in sodium excretion at high salt intake was related to the decrease in angiotensin II levels in normotensive (r = -0.43, p < 0.05), but not in hypertensive subjects (r = 0.16, n.s.). The changes in angiotensin II concentration at high salt intake were related to left ventricular mass in hypertensive (r = 0.43, p < 0.02), but not in normotensive individuals (r = 0.21, n.s.). CONCLUSION Our finding that angiotensin II concentration at high salt intake correlated with left ventricular mass independently of ambulatory blood pressure suggests that inadequate suppression of angiotensin II after high salt intake contributes to left ventricular hypertrophy already in young hypertensive individuals independently of blood pressure.

Evidence against elevated sympathetic vasoconstrictor activity in borderline hypertension.

Abstract: The relationship between sympathetic nerve activity and BP in the early stages of essential hypertension remains unclear. To investigate this relationship further, this study measured resting muscle sympathetic nerve activity (MSNA: representing peripheral vasoconstrictor activity). plasma cat- echolamines, BP, central venous pressure. and heart rate in 20 young (24 ± 2 SD yr), lean (body mass index, 24.2 ± 3.0 kg/m2), male subjects with borderline hypertension (BHT) and in 2 1 male normotensive (NT) control subjects matched for age and body mass index. A cold pressor test was also performed to evaluate sympathetic reflex responsiveness. Resting mean BP and heart rate were significantly higher in the BHT subjects compared with NT subjects ( 1 13 ± 9 versus 89 ± 9 mmHg; 74 ± 8 versus 62 ± 8 bpm; P < 0.0001 each) with no difference in central venous pressure. Resting MSNA levels tended to be lower in the BHT versus the NT group ( I 2 ± 6 versus 14 ± 9 bursts/mm, P = NS; 16 ± 8 i'e,�sus 22 ± 13 bursts/l00 heartbeats, P = 0.05) and did not correlate with either BP or body mass index. Significant positive correlations were found between resting MSNA and plasma norepinephrine levels in both groups (P < 0.05). Hemodynamic and sympa- thetic nerve responses to the cold pressor test were similar between the BHT and NT subjects. It is concluded that resting MSNA and plasma norepinephrine levels are correlated in young lean NT and BHT men; however, neither of these variables is correlated with BP. Because MSNA was similar in the two groups, the concept that augmented resting MSNA is important in the early developmental phase of essential hyper- tension must be reevaluated.

Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT3 receptors

Abstract: 1. Angiotensin (Ang) II modulates cardiovascular baroreflexes; whether or not the peptide influences chemosensitive cardiovascular reflexes is not known. We tested the hypothesis that Ang II modulates the reflex control of sympathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT3) cardiopulmonary receptors. 2. The 5HT3 receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained reflex decrease of renal sympathetic nerve activity (RSNA) but only transient (<3 min) changes of arterial blood pressure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3. Infusion of Ang II at a dose that did not affect baseline BP, HR and RSNA enhanced the PBG-evoked reflex decrease of RSNA (-54+/-5% in Ang II treated versus -33+/-6% in control rats after 15 min PBG, P<0.05, n = 6 each) in methohexital-anaesthetized rats. 4. The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the reflex responses to PBG in anaesthetized as well as conscious animals. The effect of the ACE inhibitor was abolished by concomitant infusion of Ang II. 5. The reflex response to stimulation of cardiopulmonary 5HT3 afferents was also impaired by the Ang II type 1 receptor (AT1) blocker ZD7155 but not by the type 2 (AT2) blocker PD 123319. 6. Infusion of a volume load to stimulate cardiopulmonary baroreceptors induced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA -26+/-6% in Ang II treated versus -47+/-6% in control rats after volume load, P<0.05, n = 6 each) but unaffected by ACE inhibition. 7. The reflex control of RSNA by cardiopulmonary 5HT3 receptors is enhanced by Ang II via AT1 receptors. Thus, Ang II facilitates a chemosensitive cardiovascular reflex, in contrast to its inhibitory influences on mechanosensitive reflexes.

Vasodilatory capacity of forearm resistance vessels is augmented in hypercholesterolemic patients after treatment with fluvastatin.

Abstract: Atherosclerotic vessels are characterized by endothelial and structural abnormalities as indicated by an impaired vasodilation to metabolic requirements. To determine whether effective treatment of hypercholesterolemia may improve vasodilatory capacity of resistance vessels, the authors examined the impact of 12 and 24 weeks of lipid-lowering therapy with the hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor fluvastatin (40 to 80 mg/day) on the increment in forearm blood flow during reactive hyperemia in 24 hypercholesterolemic patients (mean age: 56 +/- 11 years; 15 men/9 women). Changes in forearm blood flow in response to reactive hyperemia were measured by venous occlusion plethysmography. Serum low-density lipoprotein (LDL)-cholesterol fell from 213 +/- 32 to 125 +/- 27 mg/dL (P<0.001) after 12 weeks and remained stable at a level of 125 +/- 18 mg/dL after 24 weeks of treatment. Baseline forearm blood flow was similar before and after 12 and 24 weeks of therapy. In contrast, forearm blood flow at peak reactive hyperemia was greater at week 12 (37.0 +/- 22.9 mL/min/100 mL; P<0.05), and at week 24 (47.1 +/- 33.5 mL/min/100 mL; P<0.05) than at week 0 (30.5 +/- 18.1 mL/min/100 mL). Compared with week 0 (defined as 100%), the percent change in forearm blood flow in response to reactive hyperemia was augmented at week 12 (171 +/- 144%; P<0.05 vs week 0) and at week 24 (218 +/- 228%; P<0.05 vs week 0). Thus, the lowering of high serum LDL cholesterol after short-term treatment with fluvastatin increased the blood flow responses during reactive hyperemia in forearm resistance vessels. These data indicate a beneficial effect of HMG-CoA reductase inhibition on structural wall properties of peripheral arteries in human atherosclerosis.

Nephroprotection by antihypertensive therapy.

Abstract: Morbidity and mortality due to end-stage renal failure has become a major health concern in recent years and there is clear evidence that arterial hypertension constitutes a powerful risk factor for the progression of renal disease. Several studies have documented the benefit of blood pressure control on renal function, and it is increasingly recognized that antihypertensive therapy aimed at reducing blood pressure well below the target value of 140/90 mmHg further improves the overall renal survival rate. Different classes of antihypertensive agents show disparate specific nephroprotective properties that are unrelated to their blood pressure lowering properties. ACE inhibitors and calcium channel blockers have been reported to ameliorate renal function by favorably modifying renal and intraglomerular hemodynamics. In addition, both drugs exert beneficial effects on non-hemodynamic parameters of renal function. In contrast, beta-blockers and diuretics, although still being solely recommended as first line drugs in the management of arterial hypertension, can have adverse effects on renal function. Recently, long-term randomized controlled trials have consistently demonstrated the superior nephroprotective value of ACE inhibitors on renal function outcome. Whether AT1 receptor antagonists have similar effects on long-term renal survival is still under investigation. The outcome of forthcoming clinical trials is likely to influence clinical guidelines and optimize the medical regimen of human essential hypertension in patients with chronic renal insufficiency.