L J Verschueren

Dose response in captopril therapy of hypertension

Dose‐response curves of blood pressure and of the biochemical components of the renin‐angiotensin‐aldosterone system were determined during long‐term treatment with captopril in 21 hypertensive patients. Captopril was given in biweekly, doubling doses starting with 25 mg 3 times a day until control of blood pressure was achieved or a total daily dosage of 600 mg was reached. Recumbent and standing systolic and diastolic blood pressure fell on 75 mg captopril daily. Increasing the captopril dose did not induce further significant hypotensive effects. The pretreatment level of plasma renin activity (PRA) was a poor predictor of the hypotensive effect of captopril. The rises in PRA and plasma angiotensin I level (PA I) and the decrease in plasma angiotensin II level (PA II) and plasma aldosterone level (PAC) provide biochemical evidence for angiotensin‐converting enzyme (ACE) inhibition in vivo. These effects were present on daily doses of 75 to 150 mg captopril.

Double-blind comparison between propranolol and bendroflumethiazide in captopril-treated resistant hypertensive patients

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.

Antihypertensive therapy in patients above age 60 with systolic hypertension. A progress report of the European Working Party on High Blood Pressure in the Elderly (EWPHE)

1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.

Role of various vasodepressor systems in the acute hypotensive effect of captopril in man

SummaryThe acute hypotensive effect of captopril 25 mg was investigated in 26 hypertensive patients (11 with essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril led to an increase in plasma renin activity, active and total plasma renin concentration and angiotensin I, a decrease in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2* and no change in plasma (nor)adrenaline, dopamine and inactive renin concentration. The hypotensive effect of captopril was related to the changes in plasma angiotensin II level and inversely to the change in prostaglandin E2; the correlation coefficients were low, respectively 0.61 and −0.44. It is likely that the acute hypotensive effect of captopril to some extent is related to changes in plasma angiotensin II and in prostaglandins E2 and F2*. There is no evidence for a role of the adrenergic systems in the hypotensive response.

Functional properties of the isolated domains of Helix pomatia beta c-hemocyanin.

Hemocyanins are large copper-containing proteins. They serve as oxygen carriers in many arthropods and molluscs and display allosteric behavior. The hemocyanin of the mollusc Helix pomatia has a relative molecular mass of 9 X 106. It 75% dissociated into half molecules in 1 M NaCl or KC1 in the stability region; this fraction was called a-hemocyanin. The fraction which does not dissociate under these conditions was called /I-hemocyanin [l] consisting of a &-component which crystallizes at pH 5.3, I 10 mM, and of a &-component which remains soluble [ 2,3]. On raising the pH the components dissociate into half molecules, which yield further tenth and twentieth molecules. The polypeptide chain of &-hemocyanin consists of 8 globular domains, like beads on a string, as can be seen from electron micrographs [4]. These functional domains, designated a-h, were isolated after limited proteolysis of tenth molecules with several enzymes [5]. They contain 2 copper atoms and have a relative molecular mass of 55 000 on average. Limited trypsinolysis of the undissociated cylindrical molecules removed the collar, leaving hollow cylinders which polymerized into tubes [6]. Oxygen binding by tubes proceeded with pronounced cooperativity. The slope of the high-affinity state was significantly <l, which indicated heterogeneity of the oxygen-binding sites. Similarly tenth molecules of fl,-hemocyanin of H. pomatia showed a Hill coefficient, h, of 0.9 under non-cooperative conditions at pH 8.1 [7]. Therefore the functional domains of wall fragments

Effects of tibalosine, a new α‐adrenoceptor antagonist, in essential hypertension

Tibalosine is a phenylethylamine derivative known to lower arterial pressure in hypertensive animal models. In a double‐blind cross‐over study, 12 patients with essential hypertension, on a constant sodium intake, received placebo and tibalosine, 150 mg daily. Standing (–5.5/–6.0 mm Hg) and supine (–8.5/ –7.5 mm Hg) blood pressure and standing (– 7.0 bpm) and supine (– 7.5 bpm) pulse rate were reduced by tibalosine. Plasma renin activity (–0.41 ng/ml/hr) and plasma angiotensin 1 (—47 pg/ml) and angiotensin II (—3.0 pg/ml) levels decreased. There were no significant changes observed in plasma aldosterone or in the urinary excretion of aldosterone, kallikrein, or prostaglandin E2, F2α, and Fα metabolites. During tibalosine treatment, creatinine clearance decreased by 20 mllmin and serum creatinine rose by 0.04 mg/100 ml. The increase in serum sodium by 0.05 mmolll was not accompanied by significant changes in body weight. There were small, but significant reductions in hemoglobin (–0.4 gm/100 ml), hematocrit (– 1.5%), and erythrocyte count (–0.15 × 106 cells/mm3) during tibalosine intake, while blood glucose rose by 4.0 mg/100 ml. Apart from a slight tranquilizing effect in two anxious patients, no obvious sedation was observed. Subjective complaints were as frequent during placebo as during active treatment periods.

Effect of aspirin on renal function and the prostaglandin-kallikrein systems early after myocardial infarction

Using a double-blind procedure, 29 patients with a recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group receiving aspirin, 300 mg three times a day (n = 15) over 7 days. No change in renal function was observed in either treatment group. Compared with the placebo group, the 24-h urinary excretion of prostaglandin E2 (PGE2) was significantly suppressed in the aspirin group, but the urinary kallikrein activity was unchanged. These results contrast with our previous study of similar patients, in which sulfinpyrazone decreased renal function, as well as the urinary PGE2 and kallikrein excretions. These divergent effects of aspirin and sulfinpyrazone on urinary kallikrein activity could explain the different trends in renal function observed early after myocardial infarction.