Abstract
The effects of epoprostenol (PGI2, 2-8 ng kg-1 min-1) and 6-keto-prostaglandin E1 (6-keto-PGE1, 7.5-30 ng kg-1 min-1) on ADP-induced platelet aggregation, blood pressure (BP), heart rate and plasma renin activity (PRA) were studied in six healthy male volunteers. During graded intravenous administration of PGI2, platelet aggregation was inhibited at a minimum dose of 4 ng kg-1 min-1. The dose required to produce the same degree of platelet inhibition was approximately 15 ng kg-1 min-1 for 6-keto-PGE1. Diastolic BP was significantly reduced and PRA was increased by PGI2 at a dose greater than 8 ng kg-1 min-1. In contrast, 6-keto-PGE1 did not produce BP and PRA changes up to a dose of 30 ng kg-1 min-1. These data indicate that PGI2 has approximately four times more potent antiplatelet activity than 6-keto-PGE1 on a molar basis in man. The cardiovascular and PRA changes were less prominent for 6-keto-PGE1 than PGI2.
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Selected References
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- Berry C. N., Hoult J. R., Griffiths R. J., Moore P. K. Enzymatic inactivation of 6-keto-prostaglandin E1 in vitro: comparison with prostaglandin E1. Biochem Pharmacol. 1984 Apr 15;33(8):1277–1284. doi: 10.1016/0006-2952(84)90181-3. [DOI] [PubMed] [Google Scholar]
- Feigen L. P., Chapnick B. M., Hyman A. L., King L., Marascalco B., Kadowitz P. J. Peripheral vasodilator effects of prostaglandins: comparison of 6-keto-prostaglandin E1 with prostacyclin and escape from prostaglandin E2 in the mesenteric vascular bed. J Pharmacol Exp Ther. 1980 Sep;214(3):528–534. [PubMed] [Google Scholar]
- 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]
- Griffiths R. J., Moore P. K. Effect of 6 keto-prostaglandin E on sympathetic neurotransmission in the vas deferens. J Pharm Pharmacol. 1983 Mar;35(3):184–186. doi: 10.1111/j.2042-7158.1983.tb04305.x. [DOI] [PubMed] [Google Scholar]
- Hyman A. L., Kadowitz P. J. Vasodilator actions of prostaglandin 6-keto-E1 in the pulmonary vascular bed. J Pharmacol Exp Ther. 1980 Jun;213(3):468–472. [PubMed] [Google Scholar]
- Jackson E. K., Goodman R. P. 6-keto-prostaglandin EL and Bartter's syndrome. N Engl J Med. 1981 Jul 30;305(5):287–287. doi: 10.1056/NEJM198107303050522. [DOI] [PubMed] [Google Scholar]
- Jackson E. K., Goodman R. P., Fitzgerald G. A., Oates J. A., Branch R. A. Assessment of the extent to exogenous prostaglandin I2 is converted to 6-keto-prostaglandin E1 in human subjects. J Pharmacol Exp Ther. 1982 Apr;221(1):183–187. [PubMed] [Google Scholar]
- Jackson E. K., Herzer W. A., Zimmerman J. B., Branch R. A., Oates J. A., Gerkens J. F. 6-Keto-prostaglandin E1 is more potent than prostaglandin I2 as a renal vasodilator and renin secretagogue. J Pharmacol Exp Ther. 1981 Jan;216(1):24–27. [PubMed] [Google Scholar]
- McGiff J. C., Spokas E. G., Wong P. Y. Stimulation of renin release by 6-oxo-prostaglandin E1 and prostacyclin. Br J Pharmacol. 1982 Jan;75(1):137–144. doi: 10.1111/j.1476-5381.1982.tb08766.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyamori I., FitzGerald G. A., Brown M. J., Lewis P. J. Prostacyclin stimulates the renin angiotensin aldosterone system in man. J Clin Endocrinol Metab. 1979 Dec;49(6):943–944. doi: 10.1210/jcem-49-6-943. [DOI] [PubMed] [Google Scholar]
- 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]
- Takeda R., Morimoto S., Uchida K., Miyamori I. Changes in plasma renin activity and plasma aldosterone in the induced paralytic attack of thyrotroxic periodic paralysis. Acta Endocrinol (Copenh) 1976 Aug;82(4):715–727. doi: 10.1530/acta.0.0820715. [DOI] [PubMed] [Google Scholar]
- Wong P. Y., Lee W. H., Chao P. H., Reiss R. F., McGiff J. C. Metabolism of prostacyclin by 9-hydroxyprostaglandin dehydrogenase in human platelets. Formation of a potent inhibitor of platelet aggregation and enzyme purification. J Biol Chem. 1980 Oct 10;255(19):9021–9024. [PubMed] [Google Scholar]
- Wong P. Y., Malik K. U., Desiderio D. M., McGiff J. C., Sun F. F. Hepatic metabolism of prostacyclin (PGI2) in the rabbit: formation of a potent novel inhibitor of platelet aggregation. Biochem Biophys Res Commun. 1980 Mar 28;93(2):486–494. doi: 10.1016/0006-291x(80)91103-1. [DOI] [PubMed] [Google Scholar]
