Showing papers in "Journal of Hypertension in 1992"
Journal Article•
TL;DR: An absent or lowerNocturnal blood pressure fall in elderly hypertensives is associated with silent cerebrovascular damage, and the presence of a nocturnal fall could prevent the development of hypertensive vascular damage.
Abstract: Objective To examine the effect of diurnal blood pressure changes upon cerebrovascular damage in elderly patients with hypertension. Design Fifty-four asymptomatic hypertensive and 34 normotensive elderly subjects underwent both 24-h non-invasive ambulatory blood pressure monitoring and brain magnetic resonance imaging. METHODS. Diurnal variation was defined as a difference of greater than or equal to 10 mmHg between mean awake and asleep systolic blood pressure. Hypertensives were thus classified as dippers or non-dippers. Low intense foci (lacunae) and advanced periventricular hyperintensity were identified as silent cerebrovascular damage. Results In the hypertensive group, lacunae were correlated more closely with mean asleep systolic blood pressure than with mean awake systolic blood pressure. Age, awake blood pressure, predicted whole blood viscosity, lipid profiles or quantity of sleep did not differ between the hypertensive dippers or non-dippers. The non-dippers, however, showed significantly higher grades of cerebrovascular damage as well as cardiac hypertrophy by electrocardiography than the dippers, whose results were similar to those of normotensives in this regard. Conclusions An absent or lower nocturnal blood pressure fall in elderly hypertensives is associated with silent cerebrovascular damage. In contrast, the presence of a nocturnal fall could prevent the development of hypertensive vascular damage.
488 citations
417 citations
TL;DR: The results suggest an abnormality of basal nitric oxide-mediated dilation in the forearm arteriolar bed of patients with untreated essential hypertension.
Abstract: Objective: There is indirect evidence that the nitric oxide system may be impaired in hypertensive patients. The objective of this study was to examine basal nitric oxide-mediated dilation in hypertensive patients.Design: The forearm blood flow (FBF) response to noradrenaline and NG-monomethyl-L-arg
379 citations
TL;DR: Heavy smoking is associated with a persistent rise in blood pressure and also with an increase inBlood pressure variability, which may account for some of the smoking-related cardiovascular risk.
Abstract: Objective: To test the hypothesis that heavy smoking is associated with a persistent increase in blood pressureDesign: In 10 normotensive smokers asked to smoke one cigarette every 15 min for 1 h, blood pressure and heart rate were continuously monitored during the smoking period and during the prec
314 citations
TL;DR: The combined biochemical and genetic findings suggest that abnormalities of glucocorticoid metabolism and the renin-angiotensin system may help to explain genetic predisposition to high blood pressure.
Abstract: Aim: To assess the feasibility and utility of a new method to identify factors associated with increased predisposition to high blood pressure in young peopleSubjects: Eight hundred and sixty-four people aged 16—4 years and their parentsSetting: Ladywell Medical Centre, Edinburgh, Scotland, UK. Meth
312 citations
TL;DR: It is suggested that essential hypertension also has two mechanisms, both based upon cardiovascular hypertrophy: (1) a growth-promoting process in children (equivalent to the primary cause in secondary hypertension); and (2) a self-perpetuating mechanism in adults.
Abstract: Purpose:To review evidence that essential hypertension is a growth-related disorder with origins in childhood and manifestations in adult life.Principal evidence:Blood pressure rises with age in children and adults. In children, the rise closely relates to growth and to skeletal and sexual maturatio
234 citations
Journal Article•
TL;DR: There is increasing evidence that the local renin-angiotensin system may be involved in the maintenance of cardiovascular structure and repair, and this provides a possible mechanism for the beneficial effect of ACE inhibitors in postmyocardial infarction trials.
Abstract: BACKGROUND The renin-angiotensin system is both a circulating and a local tissue hormonal system. All components of the renin-angiotensin system have been found in important cardiovascular structures, including the heart, vessels, brain, kidney and adrenal gland. The angiotensin converting enzyme (ACE) is the final step in the enzymatic cascade of the renin-angiotensin system, which converts angiotensin in both the circulation and the tissues. IMPORTANCE OF ACE CATALYTIC SITES ACE is predominantly an ectoenzyme with a bilobed homodimer extracellular portion, a short transmembrane span and a small intracellular extension. ACE contains two catalytic sites, one on each lobe. There is evidence that these catalytic sites may differ in several properties and may have different conformational requirements. This raises the possibility that there may be different endogenous substrates for each site and it may be feasible to design more specific ACE inhibitors that inhibit only one catalytic site. CARDIOVASCULAR ROLE OF LOCAL RENIN-ANGIOTENSIN SYSTEM: The physiological cardiovascular functions of the tissue renin-angiotensin system may include regulation of regional blood flow, modulation of local sympathetic activity and interaction with the endothelium. There is increasing evidence that the local renin-angiotensin system may be involved in the maintenance of cardiovascular structure and repair. ACE is increased in many forms of vascular and cardiac hypertrophy and the administration of ACE inhibitors has led to regression of hypertrophy. Many of the beneficial effects of ACE inhibitors may be due to inhibition of the local renin-angiotensin system. ACE INHIBITION FOLLOWING MYOCARDIAL INJURY The local renin-angiotensin system may also be involved in the response to injury and in the inflammatory response. ACE is known to be increased in granulomas, it is expressed on monocytic macrophages and fibroblasts and many of the peptides involved in the inflammatory response (bradykinin, substance P, enkephalins) can act as ACE substrates. Following an acute myocardial infarct, ACE is increased in the myocardial scar and in the hypertrophying cardiac muscle. This provides a possible mechanism for the beneficial effect of ACE inhibitors in postmyocardial infarction trials. NON-CARDIOVASCULAR SYSTEM: Neither the function of the renin-angiotensin system in the brain and non-cardiovascular tissues nor its role in the pathophysiology of hypertension are known as yet.
216 citations
TL;DR: It appears that ageing exerts opposing effects on central elastic large arteries and distal muscular medium-sized arteries in hypertensives and normotensives.
Abstract: AimHypertension has been reported to accelerate the alterations in large arteries induced by ageing. Distal large arteries have been poorly investigated in contrast to proximal large arteries. The objectives of this cross-sectional study were (1) to compare the storage capacity of different arterial
209 citations
TL;DR: The proposed standardized method of measuring combined intimal and medial wall thickness in the common carotid artery appears to be a sensitive marker of vascular risk and may allow early detection and assessment of changes.
Abstract: METHODOLOGY High-resolution B-mode imaging is a reliable, easily performed and non-invasive means of studying atherosclerosis in superficial blood vessels. Recently it has been used for in vivo studies on the thickness of the common carotid artery wall. It is very sensitive, although the results of practical investigations are highly dependent on both the operator and the direction and angle of ultrasound beams directed towards the vessel. PROTOCOL We have assessed inter- and intra-observer reproducibility of the measurement of common carotid artery wall thickness in 13 subjects, using two procedures. The first was a standard echographical investigation. In the second procedure, the principal parameters recorded from the first investigation were used to reposition the beam with the same incident angle. RESULTS Intra-observer variability (correlation coefficient, r = 0.61 for procedure 1 and r = 0.77 for procedure 2) and inter-observer variation (r = 0.58 for procedure 1 and r = 0.71 for procedure 2) were reduced when the second investigation was assisted by reproducibility software. CONCLUSIONS The proposed method is a reliable and reproducible way of assessing combined intimal and medial wall thickness in the common carotid artery. It may be possible to improve reproducibility using specific software to aid the operator. Since the intimal and medial thickness of the common carotid artery appears to be a sensitive marker of vascular risk, the proposed standardized method of measuring these parameter may allow early detection and assessment of changes.
200 citations
TL;DR: Retarded growth in fetal life was strongly related to high blood pressure in adult life and was linked to impaired development in both early and late gestation.
Abstract: Aim To elucidate the fetal origins of hypertension Methods A systematic search was made for records of early growth, comprising measurements taken either at birth and/or during infancy, for groups of men and women now in middle-late life Over 25,000 men and women born before 1931 were successfully traced Results Retarded growth in fetal life was strongly related to high blood pressure in adult life Conclusion Hypertension is programmed by an adverse environment in utero It is linked to impaired development in both early and late gestation
192 citations
TL;DR: The structural basis of the mechanical properties of the arterial wall was reviewed in order to establish a coherent micro-anatomical basis for the differences in compliance among different arteries and a framework for assessing changes in the Mechanical properties of specific individual arteries in relation to changing physical stresses.
Abstract: Purpose We reviewed the structural basis of the mechanical properties of the arterial wall, in order to establish a coherent micro-anatomical basis for the differences in compliance among different arteries and a framework for assessing changes in the mechanical properties of specific individual arteries in relation to changing physical stresses. Data identification The data and concepts presented here were derived from both earlier and ongoing work. Features that assure stability and integrity in relation to blood flow (wall shear stress) and pressure (mural tensile stress) were examined. Particular attention was paid to the morphogenetic and biosynthetic means by which arteries adapt to normal or abnormal modifications of these forces, particularly in relation to growth, location in the arterial tree and geometric configuration. Results and conclusions Thickness, composition and architecture of the artery wall, including thickness and composition of the intima, are normally determined by the stresses imposed by pressure and flow. Vessel radius is closely associated with flow, so that a normal baseline level of mean shear stress of about 15 dyn/cm2 is maintained or restored. Wall thickness and composition are determined by wall tension in relation to pressure and radius. Baseline levels of tensile stress differ with location but appear to be similar for homologous vessels. Changes in flow that modify the radius also modify wall tension. Changes in wall thickness and composition are likely to cause changes in compliance, due to altered flow and/or pressure patterns; these changes in compliance may be adaptive rather than destructive. Changes in the compliance of specific arteries over time may be used to evaluate the progression and severity of the conditions underlying these changes.
TL;DR: In this paper, it is shown that ACE is increased in many forms of vascular and cardiac hypertrophy and the administration of ACE inhibitors has led to regression of hyper-trophy, which may be due to inhibition of the local renin-angiotensin system.
Abstract: BACKGROUND
The renin-angiotensin system is both a circulating and a local tissue hormonal system. All components of the renin-angiotensin system have been found in important cardiovascular structures, including the heart, vessels, brain, kidney and adrenal gland. The angiotensin converting enzyme (ACE) is the final step in the enzymatic cascade of the renin-angiotensin system, which converts angiotensin in both the circulation and the tissues.
IMPORTANCE OF ACE CATALYTIC SITES
ACE is predominantly an ectoenzyme with a bilobed homodimer extracellular portion, a short transmembrane span and a small intracellular extension. ACE contains two catalytic sites, one on each lobe. There is evidence that these catalytic sites may differ in several properties and may have different conformational requirements. This raises the possibility that there may be different endogenous substrates for each site and it may be feasible to design more specific ACE inhibitors that inhibit only one catalytic site. CARDIOVASCULAR ROLE OF LOCAL RENIN-ANGIOTENSIN SYSTEM: The physiological cardiovascular functions of the tissue renin-angiotensin system may include regulation of regional blood flow, modulation of local sympathetic activity and interaction with the endothelium. There is increasing evidence that the local renin-angiotensin system may be involved in the maintenance of cardiovascular structure and repair. ACE is increased in many forms of vascular and cardiac hypertrophy and the administration of ACE inhibitors has led to regression of hypertrophy. Many of the beneficial effects of ACE inhibitors may be due to inhibition of the local renin-angiotensin system.
ACE INHIBITION FOLLOWING MYOCARDIAL INJURY
The local renin-angiotensin system may also be involved in the response to injury and in the inflammatory response. ACE is known to be increased in granulomas, it is expressed on monocytic macrophages and fibroblasts and many of the peptides involved in the inflammatory response (bradykinin, substance P, enkephalins) can act as ACE substrates. Following an acute myocardial infarct, ACE is increased in the myocardial scar and in the hypertrophying cardiac muscle. This provides a possible mechanism for the beneficial effect of ACE inhibitors in postmyocardial infarction trials. NON-CARDIOVASCULAR SYSTEM: Neither the function of the renin-angiotensin system in the brain and non-cardiovascular tissues nor its role in the pathophysiology of hypertension are known as yet.
TL;DR: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure, casting some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.
Abstract: Objective:To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension.Design:Double-blind, placebo-controlled, parallel-group study of 28 days' duration.Setting:Three hospital outpatient departments participating i
TL;DR: A third-order, four-element modified Windkessel model can reproduce arterial pressure waveforms, including both exponential and oscillatory pressure decays observed during the diastolic portion of the cardiac cycle.
Abstract: BackgroundEngineering models of the arterial vasculature have been used to describe vascular properties of resistance and compliance. These approaches have used either Fourier frequency analysis, based on transmission line equations, or time domain analysis of the circuit equations describing modifi
TL;DR: Repeated ACE inhibitor treatment with once-daily spirapril leads to a partial escape of ACE inhibition, as reflected by a shorter duration of angiotensin II suppression, which affects the antihypertensive response in the second half of the dosing interval.
Abstract: Objective To investigate whether the compensatory rise in renin and plasma angiotensin I in response to repeated angiotensin converting enzyme (ACE) inhibitor treatment results in a partial escape of ACE inhibition over a 24-h dosing interval Design A single-blind placebo-controlled study in two parallel groups of eight hypertensive subjects receiving a once-daily dose of the ACE inhibitor, spirapril, of either 125 or 25 mg Detailed 24-h studies were performed at the end of 2 weeks of placebo, and after the first dose and 2 weeks administration of spirapril Methods Twenty-four-hour ambulatory blood pressure was measured invasively True' angiotensins I and II were measured by radioimmunoassay after high-performance liquid chromatography separation Results Both for the lower and higher doses of spirapril, the time-course of changes of spiraprilat, the active metabolite of spirapril, and ACE activity was similar but the maximal rise in angiotensin I was twofold higher after 2 weeks administration than after the first dose Angiotensin II after the first dose of spirapril fell rapidly, with lowest values 2 to 4 h after dosing At the end of dosing interval angiotensin II had returned to values seen under placebo with the 125-mg dose, but at the end of the 24-h period it was still suppressed with the 25-mg dose Compared with these first-dose responses the initial maximal degree of angiotensin II suppression after 2 weeks administration of either dose was similar, but during the subsequent hours the degree of angiotensin II suppression tended to be less with the lower and was significantly less with the higher dose of spirapril With the lower dose of spirapril responses of 24-h ambulatory blood pressure to the first dose and to 2 weeks of administration were almost superimposable, although blood pressures in the second half of the dosing interval tended to be higher during chronic treatment With the higher dose the response of nocturnal blood pressure after 2 weeks administration was diminished by 88 mmHg systolic and 68 mmHg diastolic Conclusions Repeated ACE inhibitor treatment with once-daily spirapril leads to a partial escape of ACE inhibition, as reflected by a shorter duration of angiotensin II suppression This escape also affects the antihypertensive response in the second half of the dosing interval
TL;DR: This chapter reviews the main methods used to assess the microcirculation and proposes a major role for a defect in angiogenesis as a cause of microvascular rarefaction.
Abstract: The role of the microcirculation is increasingly being recognized in the pathophysiology of cardiovascular disease. It is the major site of control of vascular resistance. In addition, the microcirculation is a major site of damage in most target organs of cardiovascular disease, such as the heart, brain, and kidney. In this chapter, we review the main methods used to assess the microcirculation. These methods include intravital microscopy, video capillaroscopy, Doppler flowmetry, and the use of isolated small arteries. Recently, important advances have been made in retinal microvascular imaging. These methods have led to important new insights in the role of changes in microcirculation both as a cause and a consequence of hypertension. We propose a major role for a defect in angiogenesis as a cause of microvascular rarefaction.
TL;DR: The changes in impedance spectra in the isolated systolic hypertensives indicate that the cross-sectional area of the peripheral vascular bed was reduced and that the aorta and large arteries were stiffer, producing an increased pulse wave velocity and an early return of pulse wave reflection in systole.
Abstract: AIM To study the determinants (or mechanisms) of isolated systolic hypertension in the elderly. METHODS Pulsatile blood pressure and flow (multisensor catheter) were measured in the ascending aorta and impedance spectra were calculated in 18 subjects undergoing cardiac catheterization. Nine subjects (mean +/- SEM age 58 +/- 1.4 years) had increased aortic systolic (166 +/- 2.3 mmHg, P < 0.001), mean (116 +/- 2.1 mmHg, P < 0.02) and pulse blood pressure (83 +/- 2.1 mmHg, P < 0.001) and normal diastolic blood pressure (84 +/- 2.0 mmHg, NS) and constituted the isolated systolic hypertension group. The other nine age-matched (58 +/- 1.1 years) subjects had normal aortic systolic and diastolic blood pressure and constituted the normotensive control group. RESULTS Both static (peripheral vascular resistance) and dynamic (characteristic impedance and wave reflection) components of left ventricular external load (aortic input impedance) were elevated in the isolated systolic hypertensives compared to the normotensive subjects; peripheral vascular resistance was 44% higher (P < 0.001), characteristic impedance (index of aortic stiffness) was 107% higher (P < 0.001), the first harmonic of impedance moduli (index of wave reflection) was 57% higher (P < 0.004) and the first impedance moduli minimum was shifted to a higher frequency (from 3.4 +/- 0.2 Hz to 4.2 +/- 0.13 Hz, P < 0.008) in the group with isolated systolic hypertension. CONCLUSIONS The changes in impedance spectra in the isolated systolic hypertensives indicate that the cross-sectional area of the peripheral vascular bed was reduced and that the aorta and large arteries were stiffer, producing an increased pulse wave velocity and an early return of pulse wave reflection in systole. The marked increase in arterial stiffness in isolated systolic hypertension offset the increase in diastolic blood pressure that would have been expected from an increase in peripheral vascular resistance alone, and early return of the reflected pressure wave augmented aortic pressure throughout systole and accounted for the large increase observed in systolic and pulse pressure in the aorta.
TL;DR: The results suggest that gluteal subcutaneous small resistance arteries of male essential hypertensive patients exhibit a decrement in responsiveness to endothelin-1, a potent vasoconstrictor peptide that may contribute to the maintenance of elevated blood pressure.
Abstract: Objective: In experimental models of hypertension in the rat, resistance arteries present a blunted response to endothelin, a potent vasoconstrictor peptide. The primary objective of this study was to investigate whether, as in hypertensive rat blood vessels, the response of human resistance arterie
TL;DR: The available data support the novel hypothesis that ouabain is an endogenous circulating agent in man and other mammals and is likely to influence long-term blood pressure levels.
Abstract: PURPOSE To review the evidence that ouabain and other digitalis-like factors are present in the human circulation under normal circumstances and in various disorders of fluid and electrolyte balance that are associated with hypertension. CONTENT Recent evidence on a number of ouabain-related issues includes (1) evidence for the existence of inhibitors of sodium pumps in mammalian plasma, (2) the identification of one of these factors as ouabain, (3) measurements of plasma levels of ouabain in man, (4) evidence that ouabain causes chronic hypertension in rats and is associated with human hypertension, and (5) data on some probable mechanisms that may mediate the pressor effect. CONCLUSIONS The available data support the novel hypothesis that ouabain is an endogenous circulating agent in man and other mammals and is likely to influence long-term blood pressure levels.
TL;DR: The data suggest that, compared with men, hypertensive women require a longer duration of exposure to high blood pressure levels during the 24 h to develop left ventricular hypertrophy.
Abstract: Objective To test the hypothesis of a difference between men and women in the left ventricular hypertrophic response to diurnal variations of ambulatory blood pressure in essential hypertension. Design Non-invasive ambulatory blood pressure monitoring and echocardiography in untreated hypertensive patients and healthy normotensive subjects. Setting Community-based ambulatory population in tertiary care centers. Patients Two hundred and sixty hypertensive patients and sixty-three healthy normotensive subjects. Main outcome measure Patients with average daytime systolic blood pressure (SBP) and diastolic blood pressure (DBP) falling by less than 10% during the night were defined as non-dippers, the others as dippers. Results In the hypertensive group, dippers and non-dippers did not differ, in either gender, in several covariates possibly affecting left ventricular structure, including daytime ambulatory blood pressure, prevalence of white coat hypertension, age, body mass index, family history and known duration of hypertension, funduscopic changes, diabetes, alcohol consumption and renal function. Left ventricular mass (LVM) did not differ between dippers and non-dippers in hypertensive men whilst in hypertensive women it was significantly lower in dippers than in non-dippers. This sex difference held for all quartiles of the distribution of mean daytime blood pressure. In hypertensive women there was an inverse correlation between LVM and the per cent reduction of SBP and DBP from day to night, but this relationship was absent in hypertensive men. Other indices of left ventricular structure differed between dippers and non-dippers in both genders, as did LVM. Conclusions For any level of daytime ambulatory blood pressure, a reduction of SBP and DBP by less than 10% from day to night identifies a subset of hypertensive patients at increased risk of left ventricular hypertrophy only in the female gender. These data suggest that, compared with men, hypertensive women require a longer duration of exposure to high blood pressure levels during the 24 h to develop left ventricular hypertrophy.
TL;DR: The results suggest that estrogen modulates angiotensinogen gene expression in a tissue-specific manner.
Abstract: OBJECTIVE Clarification of the role of estrogen in the regulation of angiotensinogen gene expression in multiple tissues. DESIGN The effect of 17 beta-estradiol (E2; 10 micrograms/100 mg body weight) administration in ovariectomized (OVX) rats upon angiotensinogen messenger RNA (mRNA) levels in multiple tissues was assessed. Confounding ovarian factors were thus removed by studying the animals in the castrate state. Controls consisted of OVX and intact female rats. METHODS Adult female Sprague-Dawley rats were ovariectomized and experiments begun 21 days postsurgery. Animals were injected with E2 and studied after 0, 1, 4, and 24 h of treatment. Levels of angiotensinogen mRNA were determined by Northern blot analysis using beta-actin mRNA as an internal standard. RESULTS A single angiotensinogen mRNA species with molecular size of approximately 1800 bp was observed in rat liver, aorta, kidney, cardiac atria, hypothalamus and whole brain. Little or no angiotensinogen mRNA was identified in the pituitary gland. Angiotensinogen mRNA was most abundant in rat liver, hypothalamus, aorta and progressively less abundant in whole brain, cardiac atria and kidney. A twofold induction of hepatic angiotensinogen mRNA levels in E2-OVX rats was observed by 4h. The angiotensinogen mRNA levels in kidney were threefold higher by 4 h compared with OVX control animals. In aorta, the angiotensinogen mRNA level was also threefold higher by 1 h after E2 treatment. No significant effect of estradiol treatment was observed in cardiac atria although the level of angiotensinogen mRNA was higher in intact female rats compared with OVX controls. CONCLUSION These results suggest that estrogen modulates angiotensinogen gene expression in a tissue-specific manner.
TL;DR: Ambulatory monitoring would decrease antihypertensive trial size by a factor of four or halve the size of a detectable DBP difference between treatments and may have led to an underestimation of the risks of minor degrees of blood pressure elevation because of a 'regression dilution' bias.
Abstract: Objective: To describe the reproducibility of diastolic blood pressure (DBP) measurement by clinic and ambulatory monitoring and to evaluate the effects of this reproducibility on the design and interpretation of clinical trials in hypertension research. Design: Prospective single-blind study of repeat measurement reproducibility of blood pressure recording. Setting: Tertiary referral hospital hypertension clinic. Patients: One hundred untreated mild-to-moderate hypertensive subjects taking 1 month of single-blind placebo. Main outcome measures: A single clinic measurement of DBP was poorly reproducible and the results for single DBP estimates taken out of a daytime ambulatory recording were similar. Average ambulatory DBP was much more reproducible, although this improvement depended upon the averaging of many measurements taken throughout the day. Conclusions: Ambulatory monitoring would decrease antihypertensive trial size by a factor of four or halve the size of a detectable DBP difference between treatments. The use of poorly reproducible DBP measurements such as single clinic readings may have led to an underestimation of the risks of minor degrees of blood pressure elevation because of a 'regression dilution' bias. For single clinic DBP readings, we calculate this underestimation to be as much as 69%, and for average ambulatory DBP approximately 20%.
TL;DR: Pvol in women with PIH was reduced compared with normal pregnancy and correlated significantly with birth weight, and can be predicted by high diastolic blood pressure, proteinuria or other clinical signs of severity, but not by haematocrit.
Abstract: Objectives: Reduction in plasma volume (Pvol) of women with pregnancy-induced hypertension (PIH; preeclampsia) has both physiological and clinical implications. This study was undertaken to determine the following variables in women with PIH: (1) the incidence of reduced Pvol; (2) the distribution of total extracellular fluid volume (ECFV); (3) the relationship between Pvol and birth weight; and (4) whether any readily available clinical or laboratory parameters predict the presence of reduced Pvol. Setting: Teaching hospital obstetric unit and antenatal clinic. Participants: Forty-nine primigravidae with PIH (28 mild, 21 severe), 54 normotensive primigravidae and 25 non-pregnant controls. Design: Pvol was measured using Evans Blue dye and ECFV as the mannitol space. These measures were compared amongst groups, and also within groups for those with PIH, according to the severity of their disorder and the presence of proteinuria or oedema. Blood pressure, haematocrit, uric acid and serum albumin were also evaluated as predictive indices of reduced Pvol in women with PIH. Results: Pvol, ECFV and the Pvol: ECFV ratio all increased during normal pregnancy. Pvol in women with PIH was reduced compared with normal pregnancy and correlated significantly with birth weight. Total ECFV was unchanged in women with PIH, but their Pvol: ECFV ratio was significantly reduced compared with normal pregnancy. Although there was a significant correlation between Pvol and haematocrit in women with PIH, haematocrit was a poor predictor for reduced Pvol. Diastolic blood pressure>100 mmHg, persistent proteinuria and severe PIH were the only reliable positive predictors of a reduced Pvol. Conclusions: Pvol is related to birth weight, but is reduced in only approximately half of women with PIH. This reduced Pvol is the result of maldistribution, not loss, of total ECFV, and can be predicted by high diastolic blood pressure, proteinuria or other clinical signs of severity, but not by haematocrit.
TL;DR: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP, and the diuretic was significantly more effective than the &bgr;‐receptor blockers.
Abstract: Objective To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. Design The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. Methods The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. Results After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. Conclusion Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.
TL;DR: The evidence suggests that the current view is not correct in relation to the cerebral circulation, and vascular hypertrophy and remodeling appear to protect cerebral vessels during hypertension, instead of being harmful.
Abstract: Aim To examine new concepts concerning structural changes in cerebral blood vessels during chronic hypertension, and to examine mechanisms that lead to cerebral vascular complications, in light of the hypothesis that hypertensive vascular hypertrophy may be harmful. Method Literature review. Results The evidence suggests that the current view is not correct in relation to the cerebral circulation. Vascular hypertrophy and remodeling appear to protect cerebral vessels during hypertension, instead of being harmful. Major cerebral vascular complications during hypertension may be largely due to endothelial dysfunction. One function of the cerebral endothelium is to serve as the blood-brain barrier. Disruption of the blood-brain barrier appears to mediate hypertensive encephalopathy. A second endothelial function is to modulate vascular tone. Abnormalities in vasoactive factors that are released by the endothelium (impaired vasodilator mechanisms and augmented vasoconstrictor mechanisms) may make an important contribution to the pathophysiology of transient ischemic episodes, and perhaps stroke, in chronic hypertension.
TL;DR: Investigation of four selective rabbit antisera developed in order to compare the distribution of immunoreactive mature endothelins and their precursors in the endothelium from human vascular tissue suggests that proendothelin-1 and proendethelin-2 must be converted to their corresponding mature peptides to produce vasoconstrictor activity in human vessels.
Abstract: OBJECTIVES We developed four selective rabbit antisera in order to compare the distribution of immunoreactive mature endothelins and their precursors, proendothelin-1, proendothelin-2 and proendothelin-3, in the endothelium from human vascular tissue. Our second aim was to use in vitro pharmacological assays to test the vasoconstrictor actions of the mature endothelin and proendothelin peptides. METHODS The antisera were shown to be selective by enzyme-linked immunosorbent assays. With these antisera, we detected immunoreactivity in serial cryostat sections from saphenous and mesenteric veins, and mesenteric and internal mammary arteries, using a peroxidase-antiperoxidase technique. In pharmacological experiments, segments of human coronary and mesenteric arteries were exposed to cumulative (0.06-60 nmol/l) concentrations of the endothelins and their precursors. RESULTS Antisera directed against mature endothelin stained the cytoplasm of endothelial cells in all vessels tested. Immunoreactive proendothelin-1 and proendothelin-2 were also detected, but not proendothelin-3. Endothelin-1 and endothelin-2 were strongly vasoactive, with similar molar potencies, and caused a dose-related increase in contractile force in human coronary arteries (0.06-60 nmol/l). However, proendothelin-1 and proendothelin-2 were 100-fold and 1000-fold less vasoactive than their respective mature peptides. No contractile effect was seen with proendothelin-3 or endothelin-3 at the concentrations tested in human coronary arteries, and similar results were obtained with human mesenteric arteries. CONCLUSIONS These results suggest that proendothelin-1 and proendothelin-2 must be converted to their corresponding mature peptides to produce vasoconstrictor activity in human vessels. Immunoreactive mature endothelin is widely distributed in human vascular endothelial cells and, if released, may produce endothelin-mediated vasoconstriction.
TL;DR: The finding of abnormal vasoconstriction in finger microcirculation in essential hypertension suggests a vasospastic tendency in the disease.
Abstract: Objective: To compare morphological and hemodynamic parameters of skin microcirculation in the fingertip in patients with essential hypertension and normotensive control subjects. Design: Consecutive sample of patients. Methods: Digital capillary blood flow measurements under normal and cooled conditions were assessed by nailfold video capillaroscopy using the technique of flying spot. Results: There was a significant reduction in capillary density in hypertensive patients, compared with normotensive subjects There was a correlation between capillary density and mean diastolic blood pressure. After local cooling, the frequency of the blood flow stop was significantly higher in hypertensive patients. Conclusion: The finding of abnormal vasoconstriction in finger microcirculation in essential hypertension suggests a vasospastic tendency in the disease.
TL;DR: The ninth Sir George Pickering memorial lecture Ambulatory monitoring and the definition of hypertension Thomas Pickering; Journal of Hypertension.
Abstract: The ninth Sir George Pickering memorial lecture Ambulatory monitoring and the definition of hypertension Thomas Pickering; Journal of Hypertension
TL;DR: Results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival.
Abstract: Objective: To study the effects of blockade of the renin—angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan.Design and methods: DSS rats (n = 186) were fed 8% NaCI from 6 to 1