Prostacyclin and Thromboxane Biosynthesis in Mild Essential Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 15; no. 5; pp. 469 - 474
• Main Authors: Minuz, Pietro, Barrow, Susan E, Cockcroft, John R, Ritter, James M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.05.1990; Hagerstown, MD Lippincott
• Subjects: Adult; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Eicosanoids - urine; Electrolytes - urine; Epoprostenol - biosynthesis; Female; Humans; Hypertension - metabolism; Hypertension - physiopathology; Hypertension - urine; Male; Medical sciences; Middle Aged; Regression Analysis; Thromboxanes - biosynthesis; Human; Hypertension; Pathophysiology; Prostaglandin I2; Arachidonic acid derivatives; Thromboxane A2; Cardiovascular disease; Arterial pressure; Essential
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.15.5.469

The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2 by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F α and 2,3-dinor-6-oxo-prostaglandin F,J and of thromboxane A2 (thromboxane B2 and 2,3-dinor-thromboxane B) using immunoafnnity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r = 0.36–0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F,a excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6- oxo-prostaglandin Fla excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p < 0.05 for diastolic pressure and 2p < 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy. In contrast, excretion rates of thromboxane B2 and 2,3-dinor-thromboxane B2 were not significantly correlated with blood pressure. We conclude that prostacyclin biosynthesis is selectively impaired in mild essential hypertension. This could contribute to the raised peripheral resistance and increased incidence of thrombosis that are characteristic of essential hypertension.