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. 1982 Jan;69(1):231–239. doi: 10.1172/JCI110435

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

Carlo Patrono 1,2,3,4, Francesco Pugliese 1,2,3,4, Giovanni Ciabattoni 1,2,3,4, Paola Patrignani 1,2,3,4, Attilio Maseri 1,2,3,4, Sergio Chierchia 1,2,3,4, Bernhard A Peskar 1,2,3,4, Giulio A Cinotti 1,2,3,4, Bianca M Simonetti 1,2,3,4, Alessandro Pierucci 1,2,3,4
PMCID: PMC371187  PMID: 7033292

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-PGF1α (the stable breakdown product of PGI2) associated with renin release induced by exogenous or pharmacologically enhanced endogenous PGI2. Intravenous PGI2 or 6-keto-PGF1α 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-PGF1α, 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-PGF1α levels rose from undetectable levels (<7.5 pg/ml) in a stepwise fashion during increasingly higher infusion rates of PGI2 or 6-keto-PGF1α. The threshold concentration of plasma 6-keto-PGF1α associated with a statistically significant stimulation of renin release was ∼200 pg/ml. Upon discontinuing PGI2 or 6-keto-PGF1α infusion, the disappearance of 6-keto-PGF1α from blood showed an identical biphasic behavior, the initial phase having an apparent t½ 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-PGF1α excretion rate, concomitant with the elevation of plasma renin activity levels, in six healthy women. 6-Keto-PGF1α 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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