The effects of angiotensin II receptor blockade with losartan on systemic blood pressure and renal and extrarenal prostaglandin synthesis in women with essential hypertension.

The major antihypertensive effect of losartan, a nonpeptide angiotensin II antagonist, is thought to be due to inhibition of the pressor effects of angiotensin II. It is possible, however, that losartan alters the synthesis of vasodilator or vasoconstrictor prostaglandins (PG), thus contributing to its antihypertensive effect. Sixteen postmenopausal women with essential hypertension, with a mean age of 59 years and diastolic blood pressures of 95 to 115 mm Hg, were enrolled in a 12-week, single-blind study to determine the effects of losartan on blood pressure, renal and extrarenal PG production, plasma renin activity (PRA), plasma aldosterone, and routine biochemical parameters. The subjects received placebo during weeks 1 to 4, 50 mg losartan daily during weeks 5 to 8, and placebo during weeks 9 to 12. During the 4-week treatment period, there were no significant, sustained changes in renal or extrarenal synthesis of PGE2, PGI2, or thromboxane A2. Losartan significantly reduced systolic blood pressure from 155 +/- 11 mm Hg (mean +/- SD) to 139 +/- 13 mm Hg (P = .001) and diastolic blood pressure from 100 +/- 2 mm Hg to 87 +/- 5 mm Hg (P < .001) despite the fact that the majority of patients had low PRA. Plasma aldosterone concentration decreased from 9.7 +/- 6.5 ng/dL to 5.1 +/- 3.9 ng/dL (P = .002) and serum uric acid declined from 4.6 +/- 0.8 mg/dL to 4.2 +/- 0.8 mg/dL (P = .018) after 4 weeks of treatment with losartan. We conclude that 1) losartan decreases blood pressure in women with essential hypertension and low plasma renin activity; 2) the antihypertensive effect is not associated with sustained changes in renal or extrarenal PG production; and 3) losartan reduces plasma aldosterone and serum uric acid concentrations in patients with essential hypertension.

RCT Entities:   Population Interventions Outcomes