1. ¹Department of Medicine, Case Western Reserve University School of Medicine, and Department of Medicine, Division of Nephrology, University Hospitals of Cleveland, Cleveland, Ohio, USA
2. ²Merck Research Laboratories, West Point, Pennsylvania, USA
3. ³Division of Pharmacological Sciences, United Medical and Dental School, Guy's and St. Thomas's Hospital, London, England

Correspondence: Michael C. Smith, MD, Department of Medicine, Division of Nephrology, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106.

^*This work was supported by a grant from Merck Research Laboratories. These data were presented in part at the American Society of Nephrology meeting, Boston, Massachusetts, November 1993.

Received 27 December 1994; Revised  0000; Accepted 12 June 1995.

Abstract

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.