Hydralazine Does Not Stimulate Prostacyclin Biosynthesis in Hypertensive Patients

The hypothesis that vascular prostacyclin synthesis is stimulated by the oral administration of hydralazine and may account for part of its vascular effect was tested. Eight white patients with mild essential hypertension were studied in a randomized, double-blind design to assess the effects of indomethacin on hydralazine’s ability to lower blood pressure, elevate pulse, and alter the vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-pros- taglandin F1α (PGF1α) measured by gas chromatography-mass spectrometry. Administration of hydralazine at either 50 mg bid or 100 mg bid for a week, doses commonly administered in clinical settings, was not associated with a statistically significant fall in mean blood pressure, although there was a tendency towards a decrease but did result in an increase in heart rate. Administration of indomethacin had no effect on the hemodynamic parameters secondary to hydralazine. Administration of indomethacin resulted in a slight but significant weight gain compared to placebo, but the addition of hydralazine did not result in a further increase in weight. Neither dose of hydralazine resulted in an increase in the urinary excretion of 2,3-dinor-6-keto-PGFlα. The excretion rate was 85 ± 16 ng/g of creatinine during placebo, 88 ± 16 ng/g of creatinine during hydralazine, 50 mg bid, and 65 ± 8 ng/g of creatinine during hydralazine, 100 mg bid. Administration of indomethacin, 50 mg bid, resulted in a significant decrease in 2,3-dinor-6-keto-PGF1α from 65 ± 6 ng/g to 37 ± 8 ng/g of creatinine. When the subjects were further subdivided into two groups, one where hydralazine administration resulted in a clearcut hypotensive response (n = 4), and in the other where there was no change in blood pressure to hydralazine (n = 4), the excretion pattern of 2,3-dinor-6-keto- PGFlα demonstrated no difference between the two groups. Our data demonstrate that when hydralazine is administered orally in usual doses, prostacyclin synthesis is not stimulated. Consequently, administration of indomethacin is not associated with any alteration of the vascular response to hydralazine.