Propranolol Increases Prostacyclin Synthesis in Patients with Essential Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 12; no. 6; pp. 582 - 588
• Main Authors: ECKMANN, MARY LEE, GERBER, JOHN G, BYYNY, RICHARD L, LOVERDE, MARY, NIES, ALAN S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.1988; Hagerstown, MD Lippincott
• Subjects: Adult; Antihypertensive agents; Biological and medical sciences; Blood Pressure - drug effects; Blood Vessels - drug effects; Blood Vessels - metabolism; Cardiovascular system; Epoprostenol - biosynthesis; Female; Humans; Hypertension - metabolism; Indomethacin - pharmacology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Propranolol - pharmacology; Therapeutic efficiency; Human; Hypertension; Prostaglandin I2; Arachidonic acid derivatives; Cardiovascular disease; Biosynthesis; Non steroidal antiinflammatory agent; Chemotherapy; Treatment; Antihypertensive agent; Drug interaction; Beta blocking agent
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.12.6.582

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drugʼs 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-dlnor-6-keto-prostaglandin F1α (PGF1α), 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-PGF1α 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-PGF1α, 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-PGF|a excretion, and it blocked the rise in urinary 2r3-dinor-6-keto-PGF1α 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-PGF1α excretion. The three nonresponders to propranolol did not display such a relationship between mean arterial blood pressure and 2,3-dinor-6-keto-PGF1α, and they had only a small increase in 2,3-dinor-6-keto-PGF1α excretion with propranolol, such that 2,3-dinor-6-keto-PGF1α 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.