PubMed Health⌕ Search

Biomedical subjects

L Link

Publications and source records attributed to L Link.

27 records · Page 2Linked to original sources
PubMed1982

Acute effects of prizidilol on blood pressure, heart rate, catecholamines, renin and aldosterone in essential hypertension.

Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (less than 107 mmHg) from 3 to 7 h and was still below predose level 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to less than 95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidiol.

Adrenergic beta-Antagonists↗
PubMed1982

Comparative evaluation of the new vasodilator carprazidil and minoxidil in the treatment of moderate to severe hypertension.

The efficacy and side effects of the new vasodilator carprazidil and the established vasodilator minoxidil were compared in 18 hypertensive patients inadequately controlled by 2 to 4 conventional drugs; the latter included diuretics, beta-blockers and/or sympatholytics and, in half the cases, vasodilators, such as hydralazine, diazoxide or the postsynaptic alpha-blocker prazosin. The vasodilators were withdrawn and, using a crossover design all patients received carprazidil (mean final dose 88 mg) and minoxidil (20 mg) for an average period of 5 to 6 months. The effects of the 2 agents appeared to be qualitatively and quantitatively similar. Both tended to cause sodium retention and an increase in heart rate, which required an increased dose of diuretic in one third of the cases or of a beta-blocker in a quarter. With this approach mean body weight and blood volume were not altered in the established phase of carprazidil or minoxidil treatment; heart rate and plasma norepinephrine tended to be only minimally increased, plasma renin was slightly increased, and plasma aldosterone and epinephrine were largely unchanged. Supine and upright blood pressure were reduced from initial values of 189/113 and 167/ 113 mm Hg, to 149/95 and 138/95 mm Hg (-18 and - 17%), respectively, during carprazidil, and to 154/95 and 141/96 mm Hg (-17 and - 15%) during minoxidil therapy. Hypertrichosis occurred with both agents in almost all patients, and limits their more prolonged use in females. No adverse side effects on haematological parameters, liver or renal function were observed, nor was antinuclear antibody detected. It is concluded that carprazidil and minoxidil are equivalent vasodilator agents in the treatment of severe hypertension, particularly in males.

Adult↗
PubMed1982

Studies on aldosterone responsiveness to angiotensin II during clinical variations in calcium metabolism in normal man.

1. Angiotensin II was infused at stepwise increasing dose rates (2, 4 and 10 pmol min-1 kg-1) in 12 normal subjects. Infusions were performed in the presence of normocalcaemia, mild hypercalcemia induced by concomitant calcium gluconate infusion, and after 2 weeks of treatment with nifedipine. 2. Pre-infusion plasma levels of angiotensin II, renin or aldosterone were not altered by acute mild hypercalcaemia or administration of nifedipine. The angiotensin II-induced increases in plasma aldosterone were also similar under the three study conditions. 3. Variations in calcium metabolism occurring under clinical conditions appear to play a minor role in modulating the angiotensin II-dependent pathway of aldosterone regulation in normal man.

Adult↗
PubMed1982

Effect of oral glucose loading on plasma insulin, potassium, renin and aldosterone in normal subjects and patients with primary hyperaldosteronism.

The effects of standard oral glucose loading (100 g) on plasma aldosterone and some regulatory factors were assessed in patients with primary hyperaldosteronism and normal subjects. Following overnight fast, mean plasma glucose was identical (10 patients and normal subjects approximately matched per age and sex); plasma insulin, potassium and renin levels were lower and plasma aldosterone higher in the patients. Glucose loading significantly increased plasma glucose and insulin concentrations and decreased plasma potassium and aldosterone levels in both groups; plasma renin activity was significantly increased only in normal subjects. The increases in plasma insulin and the decreases in plasma potassium or aldosterone tended to be blunted in primary hyperaldosteronism. Relationships among glucose-induced changes in plasma aldosterone and other factors were assessed by multiple regression analysis in these patients and normal subjects as well as an additional group of 21 normal subjects; in the latter, plasma cortisol was also measured and found to decrease significantly after glucose loading. Changes in plasma aldosterone correlated (P less than 0.025) more closely with those in plasma potassium in the patients and with variations in plasma renin activity in the normal subjects. These findings suggest that complex metabolic changes occur following glucose ingestion which are capable of modifying aldosterone secretion in normal subjects and primary hyperaldosteronism. The aldosterone-inhibitory effect of glucose tends to be blunted in the latter disorder. This could be related at least in part to an impaired insulin response in primary hyperaldosteronism.

Administration, Oral↗
PubMed1982

Effects of acute mild hypercalcemia or of the calcium antagonist nifedipine on cardiovascular responsiveness to norepinephrine or angiotensin II in normal humans.

Pressor doses of infused norepinephrine (NE) (mean pressure, +20 mm Hg) or angiotensin II (AII) (diastolic pressure, +20 mm Hg) and corresponding blood levels of NE or AII were assessed in 12 young normal subjects under basal conditions (study A), during slow calcium infusion (0.034 mg/kg/min) started 60 min previously (study C), and following 2 weeks of treatment with the Ca antagonist nifedipine, 50 mg/day (study D). Control values of blood pressure, 24-h urinary sodium, plasma NE, epinephrine, AII, and renin activity did not differ among the three studies. Plasma Ca was higher during study C than during studies A and D [10.7 +/- 0.8 (+/- SD) versus 9.1 +/- 0.3 mg/dl; p less than 0.01]. Plasma NE or AII levels obtained during NE or AII infusion as well as the pressor doses of AII were not modified by concomitant Ca infusion or following nifedipine. However, compared with basal conditions, the NE pressor dose tended to be decreased slightly during Ca infusion (106 +/- 71 versus 77 +/- 38 ng/kg/min; difference not significant) and was increased markedly following nifedipine (178 +/- 87 ng/kg/min; p less than 0.05). A control infusion of Ca alone (study B) during 120 min did not modify blood pressure or plasma renin and NE levels. Our observations suggest that in normal humans, inhibition of cellular Ca transport may predominantly affect the noradrenergic control mechanism, whereas angiotensinogenic cardiovascular regulation may be less dependent.

Adult↗
PubMedDate not supplied

Experimental acute renal artery stenosis. Dynamic CT and renal perfusion.

Unilateral renal artery stenosis of varying degrees was induced in six of seven pigs. Renal perfusion prior to and after stenosing the renal artery was determined by standard renal clearance and by the direct measurement of renal blood flow. Renal blood flow was reduced from 29 to 56% (mean 40%) in the poststenotic ischemic kidneys. A significant correlation was found between the opacification of the poststenotic ischemic kidneys after intraaortic bolus injection and direct renal blood flow (r = 0.89, P less than 0.01). There was also a significant correlation (r = 0.85, P less than 0.01) between the opacification of the kidneys and their respective glomerular filtration rates. Renal opacification determined by CT correlates significantly with renal perfusion.

Acute Disease↗
PubMedDate not supplied

Calcium and blood pressure regulation in normal and hypertensive subjects.

To elucidate the mechanisms involved in calcium-mediated blood pressure (BP) control, plasma norepinephrine (NE), epinephrine, renin activity, and angiotensin II (AII) levels and the cardiovascular pressor responsiveness to NE and AII were assessed before and during acute mild hypercalcemia or short-term calcium (Ca) inhibition with nifedipine in 20 normal and five borderline hypertensive subjects. In normal subjects, systolic BP and plasma NE and epinephrine concentrations were increased significantly (p less than 0.05) during an acute rise in serum Ca of 3.1 mg/dl (intermediate rate Ca infusion, 0.05 mg/kg/min for 3 hours), but not following an increase of 1 mg/dl (low rate Ca infusion, 0.034 mg/kg/min for 2 hours). In the borderline hypertensive group, low-rate Ca infusion elevating serum Ca by 1 mg/dl was associated with a slight increase in systolic BP (p less than 0.05) and plasma catecholamines. In both groups, the pressor responses to infused NE and AII, and plasma renin and AII levels, were unchanged during mild to moderate hypercalcemia. Nifedipine given for 2 weeks (average dose, 48 mg/d) reduced BP significantly (p less than 0.05) in the borderline hypertensive subjects only and NE pressor responses in both groups (p less than 0.025), but had no significant effect on plasma catecholamines, renin, or AII levels. These findings suggest that the adrenergic BP control mechanism may be more dependent on clinical variations in calcium metabolism than the angiotensin BP regulatory mechanism. Acute hypercalcemia may increase BP at least in part by causing an increase in adrenergic activity without an equivalent decrease in cardiovascular reactivity. Calcium inhibition with nifedipine may modify noradrenergic BP control by lowering the NE pressor reactivity without causing an equivalent increase in adrenergic activity.

Adult↗
PubMedDate not supplied

Cardiovascular counterregulation during sympathetic inhibition in normal subjects and patients with mild hypertension.

The influence of agents that inhibit sympathetic nerve activity on cardiovascular responsiveness as related to major pressor factors has been unclear. Therefore, these components were evaluated in 11 normal subjects and 13 patients with mild essential hypertension before and after 4 weeks of sympathetic neuron blockade with the agent debrisoquine. In these normal and mildly hypertensive subjects, sympathetic neuron blockade caused approximately similar decreases in urinary and supine or upright plasma norepinephrine (NE) levels (average changes in the two groups, -41% and -45%, respectively; p less than 0.05 to less than 0.005), the chronotropic dose of isoproterenol (-45% and -38%), and the NE pressor dose (-47% and -51%, p less than 0.01), while the relationship between NE-induced changes in blood pressure and concomitant plasma NE concentrations was displaced to the left (p less than 0.01). Supine heart rate was also lowered (-10% and -8%, p less than 0.05). Compared to the orthostatic variations during placebo conditions, mild postural decreases in blood pressure were apparent in both the normal and hypertensive groups (-8% and -7.5%). However, supine blood pressure was unchanged following debrisoquine treatment. Other parameters were also not consistently changed, such as total blood volume, exchangeable body sodium, urinary electrolytes, plasma epinephrine, renin, and angiotensin II (AII) levels, the pressor dose of infused AII, and the relationship between AII-induced changes in blood pressure and plasma AII measured before and during AII infusion. These findings demonstrate that the reduction in sympathetic outflow during sympathetic neuron blockade may elicit a hyperresponsiveness of alpha- and beta-adrenergic receptors that is equal in normal subjects and patients with mild essential hypertension.

Adult↗