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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 397 records · Page 22Linked to original sources
PubMed1982

[New therapeutic approaches to arterial hypertension].

Today two largely new approaches are available for the treatment of clinical hypertension. First, captopril, an orally active angiotensin converting enzyme inhibitor, makes possible chronic blockade of the renin-angiotensin system. This compound, given alone or in combination with a diuretic, normalizes the blood pressure of most hypertensive patients. Unfortunately, because captopril may induce serious adverse effects the use of this inhibitor must be restricted to patients with high blood pressure refractory to conventional antihypertensive drugs. Second, compounds such as verapamil and nifedipine are capable of producing a marked vasodilating effect by inhibiting the entry of calcium into the vascular smooth muscle cells. However, the role of calcium channel blockers in the treatment of hypertensive disease awaits more precise definition.

Angiotensin II↗
PubMed1982

Prediction of sustained antihypertensive efficacy of chronic captopril therapy: relationships to immediate blood pressure response and control plasma renin activity.

The blood pressure (BP) lowering effect of the orally active angiotensin converting enzyme inhibitor, captopril (SQ14225), was studied in 59 hypertensive patients maintained on a constant sodium intake. Within 2 hours of the first dose of captopril BP fell from 171/107 to a maximum low of 142/92 mm Hg (p less than 0.001), and after 4 to 8 days to treatment BP averaged 145/94 mm Hg (p less than 0.001). The magnitude of BP drop induced by captopril was significantly correlated to baseline plasma renin activity (PRA) both during the acute phase (r = -0.38, p less than 0.01) and after the 4 to 8-day interval (r = -0.33, p less than 0.01). Because of considerable scatter in individual data, renin profiling was not precisely predictive of the immediate or delayed BP response of separate patients. However, the BP levels achieved following the initial dose of captopril were closely correlated to BP measured after 4 to 8 days of therapy, and appeared to have greater predictive value than control PRA of the long-term efficacy of chronic captopril therapy despite marked BP changes occurring in some patients during the intermediate period. Because of these intermediate BP changes, addition of a diuretic to enhance antihypertensive effectiveness of angiotensin blockade should be restrained for several days after initiation of captopril therapy.

Adult↗
PubMed1982

Effects of the new oral angiotensin converting enzyme inhibitor MK-421 in human hypertension.

"MK-421" a new oral converting enzyme inhibitor was administered to 16 hypertensive patients in doses ranging between 2.5-40 mg once daily for periods of 6-18 weeks. The blood pressure, plasma renin activity, plasma angiotensin II, aldosterone and angiotensin converting enzyme activity were assessed before and during treatment. Blood pressure normalized in 11 patients and decreased significantly in the remaining 5, without significant changes in heart rate or orthostatic hypotension. At 24 hrs after the first effective dose, plasma renin activity remained elevated to 228% whereas plasma angiotensin II was suppressed to 58%, aldosterone was suppressed to 40% and angiotensin converting enzyme activity was suppressed to 16% of the baseline. Magnitude of blood pressure decrement achieved with the maximal dose did not correlate with baseline plasma renin activity levels. No side-effects were noted during the 6-18 week period of observation.

Administration, Oral↗
PubMed1982

Evidence for a sodium-induced activation of central neurogenic mechanisms in one-kidney, one-clip renal hypertensive rats.

The mechanisms sustaining high blood pressure in conscious one-kidney, one-clip Goldblatt rats were evaluated with the use of SK&F 64139, a phenylethanolamine N-methyltransferase inhibitor capable of crossing the blood-brain barrier and of captopril, an angiotensin converting enzyme inhibitor. The rats were studied 3 weeks after left renal artery clipping and contralateral nephrectomy. During the developmental phase of hypertension, two groups of rats were maintained on a regular salt (RNa) intake, whereas two other groups were given a low salt (LNa) diet. On the day of the experiment, the base-line mean blood pressure measured in the LNa rats (177.4 +/- 5.2 mm Hg, mean +/- S.E., n = 15) was similar to that measured in the RNa rats (178.7 +/- 5.4 mm Hg, n = 16). SK&F 64139 (12.5 mg p.o.) induced a significantly more pronounced (P less than .001) blood pressure decrease in the RNa rats (-25.6 +/- 3.6 mm Hg, n = 8) than in the LNa rats (-4.3 +/- 3.3 mm Hg, n = 7) during a 90-min observation period. On the other hand, captopril (10 mg p.o.) normalized blood pressure in LNa rats (n = 8), but produced only a 13.4 mm Hg blood pressure drop in RNa rats (n = 8). RNa rats treated with SK&F 64139 were found to have decreased phenylethanolamine N-methyltransferase activity by an average 80% in selected brain stem nuclei when compared with nontreated rats. No significant difference in plasma catecholamine levels was found between the RNa and LNa rats. These results suggest that, in this experimental model of hypertension, the sodium ion might increase the model of hypertension, the sodium ion might increase the vasoconstrictor contribution of the sympathetic system via a centrally mediated neurogenic mechanism while at the same time it decreases the renin-dependency of the high blood pressure.

Animals↗
PubMed1982

Hypertension in a patient with hypercalcemia: captopril and verapamil.

A 38-year-old woman with hypercalcemia, severe hypertension, and high renin levels was treated with the angiotensin-converting enzyme inhibitor captopril. This therapy, together with spironolactone, normalized blood pressure (BP), but even with three daily administrations of the converting enzyme inhibitor, intermittent rebound hypertension could not be avoided. The administration of only verapamil, an antagonist of calcium transport, did not induce BP control, but when verapamil therapy was combined with administration of captopril and spironolactone, BP could be normalized with only twice-daily administration of the converting enzyme inhibitor. Thus, high plasma calcium levels seem to sensitize the arterioles to the intermittent increase of angiotensin II levels that accompanies captopril therapy.

Adult↗
PubMed1981

Antihypertensive effect of the new oral angiotensin converting enzyme inhibitor "MK-421".

The effects of the new oral converting enzyme inhibitor "MK-421" on blood pressure, plasma renin activity, plasma angiotensin II, aldosterone, and angiotensin converting enzyme were assessed in 16 hypertensive patients. Maximum (maintenance) doses ranged from 2.5 mg-40 mg daily. Blood pressure decreased from 177 +/- 7/111 +/- 4 mm Hg to 145 +/- 6/94 +/- 3 mm Hg supine and from 174 +/- 7/177 +/- 4 mm Hg to 142 +/- 6/101 +/- 3 mm Hg upright (mean +/- SEM, p less than 0.001 for both). Heart rate did not change significantly. Plasma renin activity rose during treatment, whereas plasma angiotensin II, aldosterone, and angiotensin converting enzyme remained suppressed at 24h after the maximum dose. Magnitude of blood pressure reduction after the maximum dose did not correlate with baseline plasma renin activity levels. No side-effects were noted during the 2-10 week observation period. MK-421 is similar to its predecessors in efficacy and clinical and biochemical correlates, the main difference being its higher potency and longer duration of action.

Administration, Oral↗
PubMed1981

Effects of the oral angiotensin-converting enzyme inhibitor MK-421 in human hypertension.

1. The effects of the new oral angiotensin-converting enzyme (ACE) inhibitor MK-421 on blood pressure, plasma renin activity, angiotensin-II, aldosterone and converting enzyme activity were assessed in 16 hypertensive patients followed for 6--18 weeks. 2. After an initial titration period, maintenance doses of 2.5--40 mg once daily produced satisfactory blood pressure control in 11 and a partial but significant decrease in the remainder. 3. Treatment was associated with no change in heart rate and no orthostatic hypotension. At 24 h after the first effective dose, blood pressure was still decreased, plasma ACE was suppressed to 16% of the baseline, plasma angiotensin to 58%, aldosterone to 42%, and plasma renin activity was elevated to 228% of the baseline. 4. Magnitude of blood pressure fall was significantly correlated with the height of pretreatment blood pressure but not with baseline levels of plasma renin activity.

Adult↗
PubMed1981

The opposing effects of chronic angiotensin-converting enzyme blockade by captopril on the responses to exogenous angiotensin II and vasopressin vs. norepinephrine in rats.

To study the influence of acute and chronic angiotensin-converting enzyme blockade on the pressor response to exogenous angiotensin II, vasopressin and norepinephrine, we gave normal female Wistar rats 100 mg of captopril or 1 ml of 5% glucose twice daily by gavage for 2 weeks. On the 15th day, rats were anesthetized with pentobarbital, and dose-response curves to angiotensin II, lysine-vasopressin, and norepinephrine were obtained before and after intraperitoneal injection of 100 mg/kg of captopril or 1 ml of 5% glucose. Acute as well as chronic converting enzyme blockade enhanced the pressor response to exogenous angiotensin II. Similarly, sensitivity to exogenous vasopressin was increased by both acute and chronic converting enzyme inhibition. In contrast, chronic converting enzyme blockade significantly blunted the response to exogenous norepinephrine, whereas acute blockade tended to accentuate its pressor effect. These results suggest that chronic angiotensin-converting enzyme blockade may partly inhibit sympathetic activity which, in turn, might contribute to the antihypertensive efficacy of this therapeutic approach. These results also point to an important physiological interaction between the two pressor hormones, angiotensin II and vasopressin.

Angiotensin II↗
PubMed1981

Blood pressure response to central and/or peripheral inhibition of phenylethanolamine N-methyltransferase in normotensive and hypertensive rats.

We studied the effects on blood pressure and heart rate of two different phenylethanolamine N-methyltransferase (PNMT) inhibitors in normotensive, in two-kidney renal hypertensive, and in deoxycorticosterone-salt (DOC-salt) hypertensive rats. One compound (SK&F 64139) blocks the conversion of norepinephrine to epinephrine in both the central and the peripheral nervous system, whereas the other (SK&F 29661) does not cross the blood-brain barrier and therefore is active mostly in the adrenal glands. In the rats given SK&F 29661, practically no acute blood pressure changes were in the adrenal glands. In the rats given SK&F 64139 induced only a minor blood pressure and heart rate response in normotensive and two-kidney renal hypertensive rats. However, in DOC-salt hypertensive rats, it reduced arterial pressure to approximately normal levels and concomitantly slowed pulse rate. There was a close correlation between the magnitude of the blood pressure response observed in all SK&F 64139-treated animals and the control plasma norepinephrine (4 = -0.795, P less than 0.001) and epinephrine (r = -0.789, P less than 0.001) levels. These results suggest an important role for central epinephrine in regulating the peripheral sympathoadrenomedullary and the baroreceptor reflex activity, particularly when the maintenance of the high blood pressure is not renin-dependent.

Animals↗
PubMed1981

Uncontrollable hypertension in patients on hemodialysis: long-term treatment with captopril and salt subtraction.

It has been suggested that an inappropriate relationship between renin and exchangeable sodium is responsible for the hypertension of patients with chronic renal failure. Long-term blockade of the renin system by captopril made it possible to test this hypothesis in 8 patients on maintenance hemodialysis. Captopril was administered orally in 2 daily doses of 25 to 200 mg. Previously, blood pressure averaged 179/105 +/- 6/3 (mean +/- SEM) pre- and 182/103 +/- 7/3 mm HG post-dialysis, despite intensive ultrafiltration and conventional antihypertensive therapy. The 4 patients with the highest plasma renin activity normalized their blood pressure with captopril alone, whereas in the 4 remaining patients, captopril therapy was complemented by salt subtraction which consisted in replacement of 1-2 liters of ultrafiltrate by an equal volume of 5% dextrose until blood pressure was controlled. After an average treatment period of 5 months, blood pressure of all 8 patients was reduced to 134/76 +/- 7/5 mm Hg (P less than 0.001) pre- and 144/81 +/- 9/5 mm Hg (P less than 0.001) post-dialysis without a significant change in body weight. The present data suggest that captopril alone or combined with salt subtraction normalizes blood pressure of patients on chronic hemodialysis with so called uncontrollable hypertension.

Adolescent↗
PubMed1980

Enhancement by diuretics of the antihypertensive action of long-term angiotensin converting enzyme blockade.

Thirty-nine patients with various types of hypertension were treated by chronic blockage of the angiotensin converting enzyme, i.e. by twice daily administration of captopril, 50 to 200 mg p.o. The blood pressure reduction observed 1 hour following administration of the inhibitor was directly related to the baseline plasma renin activity (r=- 0.67, p < 0.001). Whenever blockade of the renin system alone did not lower blood pressure to normal levels additional sodium subtraction brought it under control. With the renin system neutralized, blood pressure becomes exquisitely sensitive to changes in sodium balance. Diuretics seem to preserve optimal natriuretic efficacy despite blood pressure reduction, probably because aldosterone levels are reduced and renal blood flow increases. Blockade of the renin system together with individually tailored salt subtraction provides an attractive new approach to long-term treatment of clinical hypertension.

Adolescent↗
PubMed1979

Improvement of chronic congestive heart-failure by oral captopril.

Catopril, an inhibitor of angiotensin converting enzyme, was given orally during cardiac catheterisation to 6 normotensive patients with refractory congestive heart-failure. 60--180 minutes after administration of 25 mg captopril, arterial pressure fell by 25%, cardiac index rose by 38%, and left-ventricular pressure and right-atrial pressure fell by 25% and 40% respectively. Plasma-renin activity rose while plasma noradrenaline and aldosterone fell. These data suggest that, in the short term, captopril can reduce both preload and afterload, and improve cardiac function, in refractory congestive heart-failure.

Administration, Oral↗
PubMed1979

Effect of captopril on renal vascular tone in patients with essential hypertension.

1. The effect of acute inhibition of angiotensin-converting enzyme by captopril (50 mg) on renal haemodynamics and function was assessed in nine patients with essential hypertension on unrestricted sodium intake (n = 8) or low sodium diet (n = 1). 2. Captopril induced a rapid and significant decrease in arterial pressure, which was maximal within 60 min. 3. Effective renal plasma flow (ERPF) increased, glomerular filtration rate (GFR) did not change and filtration fraction (FF) decreased after captopril. No change in sodium excretion and a decrease in urinary potassium occurred. 4. In the patient on low sodium diet, captopril induced striking increases in GFR and ERPF (64 and 106% respectively). 5. The logarithm of baseline plasma renin activity was positvely correlated with the change in ERPF and negatively correlated with changes in FF and renal resistance. 6. The results indicate that in patients with essential hypertension angiotensin participates actively in the maintenance of renal vascular tone at the efferent arteriolar level. A possible influence of kinins remains to be defined.

Adolescent↗
PubMed1979

Orally active angiotensin-converting enzyme inhibitor (SO 14,225) as a treatment for essential hypertension.

1 Captopril (SQ14,225), an orally active inhibitor of angiotensin-converting enzyme, was administered to nine patients with essential hypertension. Plasma renin activity (PRA) was low in four, 'normal' in three and high in two patients. 2 In the hospital, captopril alone induced a significant drop in BP from 165 +/- 6/106 +/- 2 to 140 +/- 5/90 +/- 1 mmHb (P less than 0.001). PRA increased concomitantly (P less than 0.05), whereas plasma-converting enzyme activity (P less than 0.005) and plasma aldosterone (P less than 0.05) were reduced. 3 Six patients underwent chronic ambulatory therapy with captopril for a mean of 16 +/- 3 weeks. After discharge from the hospital, BP remained normalized but in five out of six patients this required additional diuretic therapy. 4 The results suggest that captopril alone or combined with diuretic therapy provides a new, efficient and well tolerated tool to treat patients with essential hypertension independently of their PRA level. It may turn out to be more effective in lowering BP than beta-adrenoceptor-blocking agents.

Adult↗