Evidence for a Direct Stimulatory Effect of Prostacyclin on Renin Release in Man

Carlo Patrono; Francesco Pugliese; Giovanni Ciabattoni; Paola Patrignani

doi:10.1172/JCI110435

Evidence for a Direct Stimulatory Effect of Prostacyclin on Renin Release in Man

Carlo Patrono, Francesco Pugliese, Giovanni Ciabattoni, and Paola Patrignani

Published January 1, 1982 - More info

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Abstract

The objectives of this investigation were: (a) to characterize the time and dose dependence of the effects of prostacyclin (PGI₂) on renin release in healthy men; (b) to define whether PGI₂-induced renin release is secondary to hemodynamic changes; (c) to determine the plasma and urine concentrations of 6-keto-PGF_1α (the stable breakdown product of PGI₂) associated with renin release induced by exogenous or pharmacologically enhanced endogenous PGI₂. Intravenous PGI₂ or 6-keto-PGF_1α infusions at nominal rates of 2.5, 5.0, 10.0, and 20.0 ng/kg per min were performed in each of six normal human subjects; in three of them, PGI₂ infusion was repeated after β-adrenergic blockade and cyclooxygenase inhibition. PGI₂, but not 6-keto-PGF_1α, caused a time- and dose-dependent increase of plasma renin activity, which reached statistical significance at 5.0 ng/kg per min and was still significantly elevated 30 min after discontinuing the infusion. Although combined propranolol and indomethacin treatment significantly enhanced the hypotensive effects of infused PGI₂, it did not modify the dose-related pattern of PGI₂-induced renin release.

Plasma 6-keto-PGF_1α levels rose from undetectable levels (<7.5 pg/ml) in a stepwise fashion during increasingly higher infusion rates of PGI₂ or 6-keto-PGF_1α. The threshold concentration of plasma 6-keto-PGF_1α associated with a statistically significant stimulation of renin release was ∼200 pg/ml. Upon discontinuing PGI₂ or 6-keto-PGF_1α infusion, the disappearance of 6-keto-PGF_1α from blood showed an identical biphasic behavior, the initial phase having an apparent t_½ of 3.2 min. The intravenous infusion of furosemide, which is known to stimulate renin release via a cyclooxygenase-dependent mechanism, caused a three-to fourfold increase of urinary 6-keto-PGF_1α excretion rate, concomitant with the elevation of plasma renin activity levels, in six healthy women. 6-Keto-PGF_1α remained undetectable in peripheral venous plasma throughout the study.

We conclude that in human subjects: (a) PGI₂-induced renin release occurs with a dose and time dependence similar to its reported platelet effects; (b) PGI₂-induced renin release is not mediated by adrenergic stimuli or cyclooxygenase-dependent mechanisms secondary to hemodynamic changes; (c) furosemide-induced renin release is associated with increased renal PGI₂ formation; and (d) PGI₂ appears to act as a local modulator rather than a circulating hormone in controlling juxtaglomerular function.