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 (PGI2) hydrolysis product 6-keto-PGF1 alpha in the first 10 minutes after furosemide, from 17.8 +/- 2.7 ng after placebo to 34.9 +/- 7.5 ng (P less than 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 PGI2 by increased plasma renin activity 10 minutes after furosemide (6.10 +/- 1.06 vs. 3.39 +/- 0.4 ng/ml/hr; P less than 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 PGI2 synthesis and action.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004341:Drug Evaluation; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood
D006852:Hydrochlorothiazide; D015121:6-Ketoprostaglandin F1 alpha; D005665:Furosemide; D003404:Creatinine; D011464:Epoprostenol; D012083:Renin