Prostacyclin and thromboxane biosynthesis in mild essential hypertension

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(1α) and 2,3-dinor-6-oxo-prostaglandin F(1α)) and of thromboxane A₂ (thromboxane B₂ and 2,3-dinor-thromboxane B₂) using immunoaffinity 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(1α) 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 F(1α) 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.