Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 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.

Full text

PDF
231

Selected References

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

  1. Ciabattoni G., Pugliese F., Cinotti G. A., Stirati G., Ronci R., Castrucci G., Pierucci A., Patrono C. Characterization of furosemide-induced activation of the renal prostaglandin system. Eur J Pharmacol. 1979 Dec 7;60(2-3):181–187. doi: 10.1016/0014-2999(79)90217-6. [DOI] [PubMed] [Google Scholar]
  2. Ciabattoni G., Pugliese F., Spaldi M., Cinotti G. A., Patrono C. Radioimmunoassay measurement of prostaglandins E2 and F2alpha in human urine. J Endocrinol Invest. 1979 Apr-Jun;2(2):173–182. doi: 10.1007/BF03349310. [DOI] [PubMed] [Google Scholar]
  3. Demers L. M., Derck D. D. A radioimmunoassay for 6-keto-prostaglandin F1 alpha. Adv Prostaglandin Thromboxane Res. 1980;6:193–199. [PubMed] [Google Scholar]
  4. FitzGerald G. A., Friedman L. A., Miyamori I., O'Grady J., Lewis P. J. A double blind placebo controlled crossover study of prostacyclin in man. Life Sci. 1979 Aug 20;25(8):665–672. doi: 10.1016/0024-3205(79)90507-1. [DOI] [PubMed] [Google Scholar]
  5. Frölich J. C., Hollifield J. W., Michelakis A. M., Vesper B. S., Wilson J. P., Shand D. G., Seyberth H. J., Frölich W. H., Oates J. A. Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention. Circ Res. 1979 Jun;44(6):781–787. doi: 10.1161/01.res.44.6.781. [DOI] [PubMed] [Google Scholar]
  6. Frölich J. C., Wilson T. W., Sweetman B. J., Smigel M., Nies A. S., Carr K., Watson J. T., Oates J. A. Urinary prostaglandins. Identification and origin. J Clin Invest. 1975 Apr;55(4):763–770. doi: 10.1172/JCI107987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gerber J. G., Branch R. A., Nies A. S., Gerkens J. F., Shand D. G., Hollifield J., Oates J. A. Prostaglandins and renin release: II. Assessment of renin secretion following infusion of PGI2,E2 and D2 into the renal artery of anesthetized dogs. Prostaglandins. 1978 Jan;15(1):81–88. doi: 10.1016/s0090-6980(78)80006-9. [DOI] [PubMed] [Google Scholar]
  8. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  9. Hassid A., Dunn M. J. Microsomal prostaglandin biosynthesis of human kidney. J Biol Chem. 1980 Mar 25;255(6):2472–2475. [PubMed] [Google Scholar]
  10. Hensby C. N., Fitzgerald G. A., Friedman L. A., Lewis P. J., Dollery C. T. Measurement of 6-oxo-PGF1 alpha in human plasma using gas chromatography-mass spectrometry. Prostaglandins. 1979 Nov;18(5):731–736. doi: 10.1016/0090-6980(79)90093-5. [DOI] [PubMed] [Google Scholar]
  11. O'Grady J., Warrington S., Moti M. J., Bunting S., Flower R., Fowle A. S., Higgs E. A., Moncada S. Effects of intravenous infusion of prostacyclin (PGI2) in man. Prostaglandins. 1980 Feb;19(2):319–332. doi: 10.1016/0090-6980(80)90030-1. [DOI] [PubMed] [Google Scholar]
  12. Oates J. A., Whorton A. R., Gerkens J. F., Branch R. A., Hollifield J. W., Frölich J. C. The participation of prostaglandins in the control of renin release. Fed Proc. 1979 Jan;38(1):72–74. [PubMed] [Google Scholar]
  13. Patrono C., Ciabattoni G., Pinca E., Pugliese F., Castrucci G., De Salvo A., Satta M. A., Peskar B. A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980 Feb 1;17(3-4):317–327. doi: 10.1016/0049-3848(80)90066-3. [DOI] [PubMed] [Google Scholar]
  14. Patrono C., Pugliese F., Ciabattoni G., Di Blasi S., Pierucci A., Cinotti G. A., Maseri A., Chierchia S. Prostacyclin does not affect insulin secretion in humans. Prostaglandins. 1981 Mar;21(3):379–385. doi: 10.1016/0090-6980(81)90083-6. [DOI] [PubMed] [Google Scholar]
  15. Patrono C., Pugliese F. The involvement of arachidonic acid metabolism in the control of renin release. J Endocrinol Invest. 1980 Apr-Jun;3(2):193–201. doi: 10.1007/BF03348251. [DOI] [PubMed] [Google Scholar]
  16. Patrono C., Wennmalm A., Ciabattoni G., Nowak J., Pugliese F., Cinotti G. A. Evidence for an extra-renal origin of urinary prostaglandin E2 in healthy men. Prostaglandins. 1979 Oct;18(4):623–629. doi: 10.1016/0090-6980(79)90029-7. [DOI] [PubMed] [Google Scholar]
  17. Quilley C. P., Wong P. Y., McGiff J. C. Hypotensive and renovascular actions of 6-keto-prostaglandin E1, a metabolite of prostacyclin. Eur J Pharmacol. 1979 Aug 1;57(2-3):273–276. doi: 10.1016/0014-2999(79)90378-9. [DOI] [PubMed] [Google Scholar]
  18. Rosenkranz B., Fischer C., Weimer K. E., Frölich J. C. Metabolism of prostacyclin and 6-keto-prostaglandin F1 alpha in man. J Biol Chem. 1980 Nov 10;255(21):10194–10198. [PubMed] [Google Scholar]
  19. Webber P. C., Larsson C., Anggard E., Hamberg M., Corey E. J., Nicolaou K. C., Samuelsson B. Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides. Circ Res. 1976 Dec;39(6):868–874. doi: 10.1161/01.res.39.6.868. [DOI] [PubMed] [Google Scholar]
  20. Whorton A. R., Misono K., Hollifield J., Frolich J. C., Inagami T., Oates J. A. Prostaglandins and renin release: I. Stimulation of renin release from rabbit renal cortical slices by PGI2. Prostaglandins. 1977;14(6):1095–1104. doi: 10.1016/0090-6980(77)90287-8. [DOI] [PubMed] [Google Scholar]
  21. Whorton A. R., Smigel M., Oates J. A., Frölich J. C. Regional differences in prostacyclin formation by the kidney. Prostacyclin is a major prostaglandin of renal cortex. Biochim Biophys Acta. 1978 Apr 28;529(1):176–180. doi: 10.1016/0005-2760(78)90116-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES