Hydralazine does not stimulate prostacyclin biosynthesis in hypertensive patients.
The hypothesis that vascular prostacyclin synthesis is stimulated by the oral administration of hydralazine and may account for part of its vascular effect was tested. Eight white patients with mild essential hypertension were studied in a randomized, double-blind design to assess the effects of indomethacin on hydralazine's ability to lower blood pressure, elevate pulse, and alter the vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha) measured by gas chromatography-mass spectrometry. Administration of hydralazine at either 50 mg bid or 100 mg bid for a week, doses commonly administered in clinical settings, was not associated with a statistically significant fall in mean blood pressure, although there was a tendency towards a decrease but did result in an increase in heart rate. Administration of indomethacin had no effect on the hemodynamic parameters secondary to hydralazine. Administration of indomethacin resulted in a slight but significant weight gain compared to placebo, but the addition of hydralazine did not result in a further increase in weight. Neither dose of hydralazine resulted in an increase in the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha. The excretion rate was 85 +/- 16 ng/g of creatinine during placebo, 88 +/- 16 ng/g of creatinine during hydralazine, 50 mg bid, and 65 +/- 8 ng/g of creatinine during hydralazine, 100 mg bid. Administration of indomethacin, 50 mg bid, resulted in a significant decrease in 2,3-dinor-6-keto-PGF1 alpha from 65 +/- 6 ng/g to 37 +/- 8 ng/g of creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerber
J G
JG
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Beckmann
M L
ML
Loverde
M
M
Byyny
R L
RL
Nies
A S
AS
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D006830:Hydralazine; D011464:Epoprostenol; D007213:Indomethacin