Antihypertensive efficacy of low dose torasemide in essential hypertension: a placebo-controlled study.

The blood pressure lowering effect of chronic treatment with the low, non-diuretic dose of 2.5 mg of torasemide, a new loop-diuretic, was assessed in 20 patients with mild to moderate essential hypertension (WHO stage I-II) in a randomised, double-blind, balanced, placebo-controlled, cross-over study. Blood pressure was significantly reduced after four weeks of torasemide as compared to four weeks of placebo. No significant diuretic effect was detected and there were no relevant metabolic or clinical side effects. The present results show that torasemide 2.5 mg once daily has a significant BP lowering effect and is well tolerated in patients with mild to moderate hypertension. This low dose, lacking significant diuretic activity, appears to be the recommended dose for starting antihypertensive treatment with this compound.

Hypotensive and regional haemodynamic effects of fenoldopam and quinpirole in the anaesthetized rat.

The effects of systemic administration of the selective dopamine1 receptor agonist fenoldopam and the selective dopamine2 receptor agonist quinpirole on blood pressure and regional haemodynamics were investigated in anaesthetized normotensive Wistar rats. Both compounds produced dose-dependent reductions in blood pressure. Mesenteric and renal blood flow were enhanced by fenoldopam, but reduced by quinpirole. Hindquarter blood flow was not modified by fenoldopam, but was increased by quinpirole. The calculated vascular resistances were reduced by both compounds in the three vascular beds. The effects of fenoldopam were antagonized by SCH 23390 but SCH 23390 did not affect those of quinpirole. The effects of quinpirole, but not those of fenoldopam, were antagonized by domperidone. Hexamethonium abolished the effects of quinpirole without affecting those of fenoldopam. These results indicate that the hypotensive effects of fenoldopam and quinpirole are due to stimulation of postsynaptic dopamine1 and neuronal dopamine2 receptors, respectively, resulting in differential regional haemodynamic effects.

Placebo does not lower ambulatory blood pressure.

The effects of 4 weeks of placebo on clinic and on ambulatory blood pressure, measured non-invasively using the Remler M 2000 portometer, were studied in 46 hypertensive patients who were included in three consecutive double-blind randomized placebo-controlled trials with antihypertensive drugs. Placebo significantly reduced clinic blood pressure, but had no significant effect on ambulatory blood pressure.

Effect of guanfacine on ambulatory blood pressure and its variability in elderly patients with essential hypertension.

The effect of guanfacine (2 mg once daily) on ambulatory blood pressure was studied with the Remler M 2000 recorder in 16 elderly hypertensive patients during a randomized, double-blind, placebo-controlled, balanced, cross-over study. Guanfacine significantly reduced heart rate and systolic and diastolic ambulatory blood pressure. The antihypertensive effect was maintained over the whole recording period. Systolic and diastolic blood pressure variability was not changed by guanfacine, neither when defined as standard deviation or variation coefficient of the mean, nor when defined as the range between the highest and lowest ambulatory blood pressure, suggesting that blood pressure variability is unrelated to sympathetic nervous system activity.

Improved renal function during chronic lisinopril treatment in moderate to severe primary hypertension.

The effect of the converting enzyme inhibitor lisinopril on renal and cardiac hemodynamics was studied in patients with moderate to severe primary hypertension, in a multicenter, double-blind, randomized clinical trial comparing the antihypertensive effect of lisinopril (LIS) and nifedipine (NIF). After a 2 week placebo run-in period, 15 patients were randomized in a 2:1 ratio to receive either LIS (20-80 mg q.d., n = 10) or NIF (20-40 mg b.i.d., n = 5). LIS significantly reduced blood pressure (BP) without changing heart rate or cardiac output. LIS significantly increased renal blood flow; glomerular filtration rate (GFR) was not changed. It can be concluded that LIS is an effective antihypertensive agent with a favorable renal hemodynamic profile.

Effect of carvedilol on ambulatory blood pressure, renal hemodynamics, and cardiac function in essential hypertension.

A randomized, double-blind, placebo-controlled study was set up to study the effects of acute and chronic administration of carvedilol, a vasodilatory beta-blocker in essential hypertension. Acute administration of a single dose of 50 mg of carvedilol reduced systolic and diastolic blood pressure, without inducing reflex tachycardia. Renal blood flow was preserved; accordingly renal vascular resistance was significantly reduced. A significant reduction of glomerular filtration rate and filtration fraction was observed. Plasma renin activity (PRA) and plasma aldosterone were not changed. Chronic carvedilol treatment produced a significant fall in systolic and diastolic office and ambulatory blood pressure, heart rate, cardiac output, PRA and plasma aldosterone. Blood pressure variability was not changed. Renal blood flow, glomerular filtration rate and filtration fraction also remained unchanged; renal vascular resistance decreased significantly. It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties, both acutely and after chronic treatment.

Noninvasive ambulatory monitoring of blood pressure in essential hypertension. Effect of age on variability and disparity.

Noninvasive daytime ambulatory blood pressure monitoring using the Remler M 2000 Portometer was performed on 84 hypertensive patients to study the effects of age on blood pressure variability and on disparity between office and ambulatory blood pressure. Disparity was higher in younger (less than 30 years) and in older (greater than 60 years) subgroups, as compared with middle-aged (30-60 years) patients. Disparity correlated with age in those greater than 30 years and increased with increasing office blood pressure. Systolic blood pressure, but not diastolic blood pressure, correlated with its variability. In patients greater than 30 years old, diastolic, but not systolic, variability correlated with age. Both, the younger and the older patients showed a higher blood pressure variability as compared with middle-aged patients. Variability and disparity were unrelated to sex.

Effect of fenoldopam on the aldosterone response to metoclopramide in man.

The effect of fenoldopam, a selective DA1-agonist, on the plasma aldosterone response to metoclopramide was studied in six hypertensive patients included in a multicentre double-blind placebo controlled cross-over study of the antihypertensive effects of fenoldopam. Fenoldopam significantly increased baseline plasma renin activity (PRA); baseline plasma aldosterone levels rose slightly. Baseline PRL and the PRL response to metoclopramide were not altered by fenoldopam. After metoclopramide, a significant increase of plasma aldosterone was observed during treatment with fenoldopam, as well as in the placebo-period. The peak values were not significantly different and occurred at 15 min during both treatment periods. These results indicate that fenoldopam does not reduce metoclopramide-induced aldosterone secretion and therefore suggest that the adrenal dopamine receptor is not identical to the vascular DA1 receptor.

Nadolol in essential hypertension: effect on ambulatory blood pressure, renal haemodynamics and cardiac function.

Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double-blind, placebo-controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

Clonidine-suppression test in epinephrine secreting pheochromocytoma: report of a case.

A patient is described in whom the diagnosis of pheochromocytoma was suspected on clinical grounds. He had normal urinary and plasma norepinephrine levels, with normal suppression of plasma norepinephrine by clonidine. However, plasma and urinary epinephrine levels were above normal, and plasma epinephrine was not suppressed but increased by clonidine. Selective venous sampling showed marked unilateral adrenal epinephrine excess. A large epinephrine secreting pheochromocytoma was surgically removed. This case suggests that, in pheochromocytomas releasing predominantly epinephrine, normal norepinephrine release from axon terminals of sympathetic postganglionic neurons is maintained and is suppressed by clonidine administration. It further reaffirms the value of plasma epinephrine estimations in the diagnosis of pheochromocytoma and indicates that normal suppression of plasma norepinephrine by clonidine does not preclude the presence of a predominantly epinephrine secreting tumor.

Stimulation of aldosterone secretion by metoclopramide is not affected by chronic converting enzyme inhibition.

To assess if dopaminergic control of aldosterone secretion is mediated by the renin-angiotensin system, the effect of chronic angiotensin converting enzyme inhibition by enalapril on the aldosterone response to metoclopramide has been studied in 10 patients with mild to moderate essential hypertension. Enalapril reduced supine blood pressure and increased the heart rate significantly. Plasma renin activity and urinary sodium excretion rose significantly. PRA was not changed by metoclopramide, neither during placebo nor during enalapril treatment. Metoclopramide induced a two-fold increase in plasma aldosterone, the peak response being reached within 15 min. Enalapril treatment did not alter the aldosterone response to metoclopramide. Dopaminergic control of aldosterone secretion appears to be independent of the renin-angiotensin system.

Weber-Christian panniculitis with membranous glomerulonephritis.

A case of Weber-Christian panniculitis is described in which an acute phase of the disease was accompanied by the presence of circulating immune complexes, elevated serum levels of IgA and IgM, and membranous glomerulonephritis, with concomitant spontaneous remission of both diseases. This case reinforces the view that an immunologic dysfunction may be involved in the pathogenesis of Weber-Christian panniculitis.