The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period ...on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The intra-erythrocyte and intra-leucocyte Na+ concentration was increased by 11 and 7%, respectively, during xipamide administration, while the intracellular K+ concentration was decreased by 3 and 4%, respectively. No significant effect of xipamide could however be demonstrated on the ouabain-sensitive, bumetanide-sensitive or ouabain-bumetanide-resistant 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+-Li+ countertransport was also not changed in the xipamide-treated subjects. Our data suggest that the increased intracellular Na+ concentration and the decreased K+ concentration in red and white blood cells of xipamide-treated subjects cannot be attributed to changes in the activity of the Na+ pump, the Na+-K+ cotransport or Na+-Li+ countertransport system or to changes in the number of active Na+ pump units.
1 Labetalol was administered to 18 hypertensive patients for an average duration of 2.44 weeks, with an average final daily dose of 1.65 g (principally to study its short‐term haemodynamic effects). ...2 Labetalol decreased resting heart rate by 16% and maximal exercise heart rate by 21%; the phenylephrine‐induced increase in systolic brachial arterial pressure was reduced by 36%. 3 During labetalol treatment brachial arterial pressure was decreased by 29/15 mmHg in the recumbent position, by 41/23 mmHg at rest sitting and by 53/23 mmHg at maximal exercise; total peripheral resistance was not significantly affected at rest recumbent but was reduced at sitting and at exercise; cardiac output was decreased in all conditions. 4 Labetalol reduced mean pulmonary arterial and capillary wedge pressures only in the sitting position. Pulmonary vascular resistance remained unchanged. 5 The drug produced significant decreases in plasma renin activity and in plasma aldosterone concentration.
In a double-blind crossover trial, 15 captopril (daily dose 600 mg) treated patients received in addition to the converting enzyme inhibitor, placebo, propranolol (240 mg), or bendroflumethiazide ...(7.5 mg). Propranolol produced an additional hypotensive effect, while pulse rate slowed, indicating effective beta-adrenoceptor blockade. Plasma renin activity decreased, but the hypotensive effect of propranolol was not accompanied by changes in the plasma angiotensin II and aldosterone levels or in the urinary aldosterone excretion. Also bendroflumethiazide lowered blood pressure, while body weight decreased slightly. During captopril-bendroflumethiazide treatment, serum sodium and potassium decreased while the plasma renin-angiotensin-aldosterone system was stimulated. In these captopril-treated patients, the hypotensive response to bendroflumethiazide tended to be somewhat larger than the response to propranolol, but the difference was small and statistically not significant.
Variants of the human genes coding for renin, angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and the angiotensin II type-I receptor (AT1R) are inconsistently associated with ...cardiovascular-renal disease, possibly because of genetic differences in the background populations.
This systematic review of the literature investigated genetic variation in the renin system according to race, sex and age. Across studies with relevant information, multivariate analyses also accounted for the methods of genotyping and the enrollment of subjects as controls, cases or groups studied cross-sectionally.
The 185 reviewed reports included 64978 subjects. In five studies (n=989) on the renin gene, the Hind III and Taq I polymorphisms varied with the groups' average age, whereas the Bg I, Bg II and Hind III but not Taq I sites differed according to race. Among 135 studies (n=44697) on the deletion/insertion (D/I) polymorphism of the ACE gene, the frequency of the D allele was 54.0%. Its prevalence was not related to sex and black race, was 49.9% lower in Asians, 10.0% lower in studies relying on I-specific primers, 4.9% higher for each 25-year increment in the average age of the groups studied, and 16.7% higher in cases than controls. Among 12 studies (n=4952) on the T174-->M variant of the AGT gene, the M174 frequency was 11.0%, did not vary according to sex and enrollment group, was 56.7% lower in blacks and 39.5% lower for each 25-year increase in the groups' mean age. Across 44 studies (n=16713) on the M235-->T substitution in the AGT gene, the T235 prevalence was 51.6%. Its frequency was not related to sex and the method of genotyping, tended to be 7.5% lower for each 25-year increase in average age, was from 4.6 to 6.6 times higher in nonwhites than whites and 13.2% higher in cases than controls. Among 13 studies (n=4332) on the A1166-->C variant of the AT1R gene, the C1166 allelic frequency was 25.7%. Its prevalence was independent of the enrollment group, 77.4% lower in Asians, and nearly doubled for each 25-year increment in age.
With adjustments applied for the subjects' enrollment group and the methods of genotyping, genetic polymorphism in the renin system varies according to race and age, but not sex. One possible application of the present results is to provide allelic and genotypic frequencies, which could be used to assess power, to perform sample size calculations, or to predict selection bias in future studies.
The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ...ketanserin on another occasion. The effects of ketanserin on the components of the renin-angiotensin-aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.
The intraerythrocyte sodium concentration is increased in the erythrocytes of Zaïrean Bantu with untreated hypertension, while the red blood cell potassium is not different from that of normotensive ...subjects. Compared with whites, normotensive healthy blacks have a higher intracellular concentration of sodium due to a depressed activity of the sodium-potassium pump. Normotensive healthy males with a positive familial background of hypertension display higher erythrocyte sodium and lower cotransport activity. None of the two measurements offer a clear-cut genetic marker of essential hypertension. In healthy women, the erythrocyte sodium concentration is lowered during the luteal as compared with the follicular phase of the menstrual cycle. This variability explains the difference observed between men and women. A low-sodium diet stimulates the activity of the sodium-potassium ATPase pump, which leads to a decrease in the erythrocyte sodium concentration. Both alterations reverse only slowly during sodium repletion. It is therefore suggested that an adequate matching for race, sex, stage of the menstrual cycle (in women), family history of hypertension, and the amount of sodium in the diet should be a prerequisite for valid conclusions when interpreting the erythrocyte concentration and fluxes of sodium.
To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either ...normotensive or hypertensive by conventional blood pressure (CBP) measurement.
Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (systolic CBP < or = 140 mmHg and diastolic CBP < or = 90 mmHg) and 1773 were hypertensive (systolic CBP > or = 160 mmHg and/or diastolic CBP > or = 90 mmHg). Of the latter, 1324 had systolic and 1310 had diastolic hypertension.
Ninety-five percent of the normotensive subjects had a 24-h ABP below (systolic and diastolic, respectively) 133 and 82 mmHg. Of the patients with systolic hypertension, 24% had a 24-h systolic ABP of < 133 mmHg. Similarly, 30% of those with diastolic hypertension had a 24-h diastolic ABP of < 82 mmHg. The probability that hypertensive patients had a 24-h ABP below these thresholds was higher in women than in men, increased with age and was 2- to 4-fold greater if the CBP of the patient had been measured at only one visit and if fewer than 3 CBP measurements had been averaged to establish the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for the 24-h systolic ABP and by 25% for the 24-h diastolic ABP, and for each 5 mmHg increment in diastolic CBP it increased by 6 and 9%, respectively.
The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of the hypertensive patients had an ABP which was below the 95th centile of the ABP in normotensive subjects, but this proportion decreased if the hypertensive patients had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.
CP-804-S is a substituted phenylbutylamine, known to lower arterial pressure in hypertensive animal models. In a double-blind, crossover study, 12 patients with essential hypertension receiving a ...constant sodium intake received placebo and CP-804-S, 150 mg daily. Standing (–5.5/– 6.0 mm Hg) and supine (– 8.5/– 7.5 mm Hg) blood pressures and standing (– 7.0 beats/min) and supine (– 7.5 beats/min) pulse rates were significantly reduced by CP-804-S. Plasma renin activity (– 0.41 ng/ml/hr) and plasma angiotensin I (– 47 pg/ml) and angiotensin II (– 3.0 pg/ml) levels decreased significantly. No significant changes were observed in plasma aldosterone or in the urinary excretion of aldosterone, kallikrein, and prostaglandin E2, F2α, and Fα metabolite.
CP-804-S is a substituted phenylbutylamine, known to lower arterial pressure in hypertensive animal models. In a double-blind,
crossover study, 12 patients with essential hypertension receiving a ...constant sodium intake received placebo and CP-804-S,
150 mg daily. Standing (â5.5/â6.0 mm Hg) and supine (â8.5/â7.5 mm Hg) blood pressures and standing (â7.0 beats/min) and supine
(â7.5 beats/min) pulse rates were significantly reduced by CP-804-S. Plasma renin activity (â0.41 ng/ml/hr) and plasma angiotensin
I (â47 pg/ml) and angiotensin II (â3.0 pg/ml) levels decreased significantly. No significant changes were observed in plasma
aldosterone or in the urinary excretion of aldosterone, kallikrein, and prostaglandin E 2 , F 2α , and F α metabolite.
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