Propranolol increases prostacyclin synthesis in patients with essential hypertension.
We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and 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), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Beckmann
M L
ML
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Gerber
J G
JG
Byyny
R L
RL
LoVerde
M
M
Nies
A S
AS
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology*
D011433:Propranolol; D011464:Epoprostenol; D007213:Indomethacin