The antihypertensive action of hydrochlorothiazide and renal prostacyclin

To investigate whether chronic hydrochlorothiazide (HCTZ) therapy increases synthesis of tissue vasodilator prostaglandins (PG), we used intravenous furosemide as a standardized stimulus of renal PG synthesis before and after HCTZ dosing. Sixteen subjects with mild hypertension received placebo for 4 weeks, followed by HCTZ, 50 mg/day, and potassium chloride, 60 mmol/day, for 4 weeks. Nine subjects had decreased mean arterial pressure (−12.2 ± 0.9 mm Hg) after HCTZ (responders), while seven others had no antihypertensive effect (nonresponders). Responders increased their excretion of the prostacyclin (PGI 2 ) hydrolysis product 6‐keto‐PGF 1α in the first 10 minutes after furosemide, from 17.8 ± 2.7 ng after placebo to 34.9 ± 7.5 ng (P < 0.05) after HCTZ, whereas nonresponders showed no such increase. These groups could not be distinguished on the basis of sex, age, or pretreatment plasma renin activity. After HCTZ dosing, responders showed evidence of increased action of PGI 2 by increased plasma renin activity 10 minutes after furosemide (6.10 ± 1.06 vs. 3.39 ± 0.4 ng/ml/hr; P < 0.05). Furthermore, creatinine clearance was maintained in responders (while decreasing slightly in nonresponders) despite lower blood pressure, a finding consistent with increased vasodilator effect. We conclude that an antihypertensive response to HCTZ is accompanied by an increase in renal PGI 2 synthesis and action. Clinical Pharmacology and Therapeutics (1986) 39, 94–101; doi: 10.1038/clpt.1986.16