Propranolol increases prostacyclin synthesis in patients with essential hypertension.

Publisher Website
Google Scholar
Abstract
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 ranodmized, double-blind design to assess the effects of indomethacin with or wihtout 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.), 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. The patients with an antihypertensive response to propranolol had a significant negative correlation between their baseline mean arterial blood pressure and 2.3-dinor-6-keto-PGF1.alpha. excretion. The three nonresponders to propranolol did not display such a relationship between mean arterial blood pressure and 2,3-dinor-6-keto-PGF1.alpha., and they had only a small increase in 2,3-dinor-6-keto-PGF1.alpha. excretion with propranolol, such that 2,3-dinor-6-keto-PGF1.alpha. levels remained significantly less than mean normal values, even in the face of propranolol therapy. These findings suggest that enhanced synthesis of prostacyclin is associated with the full antihypertensive effect of propranolol. In addition, the hypertensive effect of indomethacin, by whatever mechanism, blunts the full antihypertensive response to propranolol.