Blood Pressure Lowering Effect Of Captopril Research Articles

Possible impact of nitric oxide on the antihypertensive effect of captopril and zaprinast.

The interaction between the renin-angiotensin system and nitric oxide (NO) is undeniable, but its nature is not fully known. This study investigated the contribution of NO to the acute hypotensive effect of captopril in conscious normotensive rats and the effect on blood pressure of dual administration of captopril and the phosphodiesterase-5 inhibitor zaprinast. In two separate experiments, rats were pretreated with the NO inhibitor L-arginine methyl ester (L-NAME) and with the NO enhancer zaprinast. Pretreatment with L-NAME attenuated and pretreatment with zaprinast potentiated the hypotensive effect of captopril. The hypotensive effect of captoril was not associated with a significant change in the plasma level of cyclic guanosine monophosphate (cGMP). These findings suggest that NO contributes to the blood pressure-lowering effect of captopril. The inability of captopril to alter plasma cGMP levels is not consistent with this view, however, and leads to the conclusion that NO contributes to the acute hypotensive effect of captopril, although the mechanism is not fully understood. Zaprinast potentiates the hypotensive effect of captopril, and an adjustment in dose should be considered when this combination is administered.

Aspirin enhances the antihypertensive effect of captopril in spontaneously hypertensive rats.

Activation of renal or vascular prostaglandin mechanisms (or both) has been proposed to contribute to the antihypertensive action of captopril. In conscious spontaneously hypertensive rats (SHR) studied in the established phase of hypertension, the blood pressure-lowering effect of captopril, 30 mg/kg/12 hr p.o. given for 7 days, was greatly enhanced by the addition of aspirin, 200 mg/kg/day s.c. Systolic blood pressure decreased from 185 +/- 6 and 182 +/- 4 to 135 +/- 3 mm Hg in rats treated, respectively, with captopril and aspirin or captopril alone, and was unaltered by either vehicle or aspirin alone. Water intake was inconsistently affected by captopril but was increased (p less than 0.01) by aspirin and was even higher after captopril-aspirin treatment (p less than 0.01). Urine volume was elevated in all 3 drug-treated groups, increasing threefold after captopril-aspirin treatment. Excretion of sodium and potassium was unchanged by any treatment regimen. In the vehicle group, prostaglandin F2 alpha excretion, measured by radioimmunoassay, ranged between 65 and 93 ng/8 hr and was twofold to fourfold higher than that of prostaglandin E2. Prostaglandin F2 alpha was unaffected during captopril treatment, whereas prostaglandin E2 excretion decreased to 12 +/- 2 ng/8 hr (p less than 0.01) by Day 7. Long-term aspirin treatment, either with or without captopril, did not cause sustained inhibition of renal prostaglandin excretion, although a transient effect occurred within the first four hours of administration. These results indicate 1) aspirin potentiates the blood pressure-lowering effect of captopril in SHR, an effect that is associated with a threefold increase in urine flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril treatment in hypertensive dialysis patients.

Captopril was used for treatment resistant arterial hypertension in 17 dialysis patients. Excellent blood-pressure control with diastolic blood-pressure less than 95 mmHg was obtained in 10 out of 17 patients (59%), with captopril as only drug in 8 patients. Six patients have been treated more than 6 months and 4 patients have been on the treatment for 1 year. The dosage of captopril could be kept low with maintained antihypertensive and angiotensin converting enzyme blocking effects. The acute blood-pressure lowering effect of captopril in dialysis patients was correlated to the initial plasma renin activity (p less than 0.001) but not long-term treatment, which was successful also in several low-renin patients. A few adverse reactions were encountered, e.g. urticaria and bullous exanthema, but all resolved when captopril treatment was stopped. Plasma potassium increased only from 4.8 +/- 0.1 to 5.0 +/- 0.1 mmol/l at the end of 1 month's treatment. Captopril appears to be a valuable drug for treatment of arterial hypertension in dialysis patients and offers an alternative to bilateral nephrectomy for the management of treatment resistant hypertension in these patients.

Absence of blood-pressure lowering effect of captopril in anephric patients.

Captopril, an orally active inhibitor of angiotensin-I-converting enzyme, was administered in a single dose to five anephric patients who had extremely low plasma renin activities. The drug did not lower blood pressure or significantly alter plasma renin activity in any patient but increased mean arterial pressure slightly in three. These results suggest that the blood-pressure lowering effect of captopril depends on an active renal renin-angiotensin system. Though additional mechanisms, such as accumulation of vasodilator kinins resulting from kininase II inhibition, may also contribute to captopril's action, these mechanisms apparently require the presence of the kidney to have a clinically detectable effect.