Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jul;75(7):3522–3526. doi: 10.1073/pnas.75.7.3522

Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with prostacyclin and other prostanoids.

A L Hyman, P J Kadowtiz, W E Lands, C G Crawford, J Fried, J Barton
PMCID: PMC392810  PMID: 356056

Abstract

The effects of a recently synthesized, stable prostacyclin (PGI2) analog, 13,14-dehydro-PGI2 methyl ester, and authentic PGI2 and several other prostanoids on the coronary circulation were investigated in the intact dog by using a new technique to measure coronary sinus blood flow. The PGI2 analog, PGI2, and prostaglandin (PG) E2 and D2 each increased coronary sinus blood flow in a dose-related fashion when injected into the left coronary artery. The analog and PGE2 had similar vasodilator activity while PGI2 was slightly more potent. PGD2 was a moderately active coronary vasodilator whereas PGF2alpha was inactive. The coronary vasodilator effects of PGI2, its analog, PGE2, and PGD2 occurred at doses that had little effect on aortic pressure, left ventricular pressure and its first derivative, or on cardiac output and heart rate. The prostaglandin precursor arachidonic acid and the endoperoxide intermediate PGH2 both increased coronary sinus blood flow in a dose-dependent manner. The effects of arachidonic acid were inhibited by indomethacin. These data show that PGE2, PGI2, and a stable PGI2 analog are potent vasodilators in the canine coronary vascular bed and suggest that the vasodilator effects of arachidonic acid and PGH2 may be due to the formation of PGE2, PGD2, or PGI2 in the dog heart.

Full text

PDF
3522

Images in this article

3523Image
on p.3523

Selected References

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

  1. Bunting S., Gryglewski R., Moncada S., Vane J. R. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac ateries and inhibits platelet aggregation. Prostaglandins. 1976 Dec;12(6):897–913. doi: 10.1016/0090-6980(76)90125-8. [DOI] [PubMed] [Google Scholar]
  2. Chapnick B. M., Paustian P. W., Feigen L. P., Joiner P. D., Hyman A. L., Kadowitz P. J. Influence of inhibitors of prostaglandin synthesis on renal vascular resistance and on renal vascular responses to vasopressor and vasodilator agents in the cat. Circ Res. 1977 Apr;40(4):348–354. doi: 10.1161/01.res.40.4.348. [DOI] [PubMed] [Google Scholar]
  3. Dusting G. J., Moncada S., Vane J. R. Prostacyclin (PGI2) is a weak contractor of coronary arteries of the pig. Eur J Pharmacol. 1977 Oct 1;45(3):301–304. doi: 10.1016/0014-2999(77)90014-0. [DOI] [PubMed] [Google Scholar]
  4. Dusting G. J., Moncada S., Vane J. R. Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachindonic acid. Prostaglandins. 1977 Jan;13(1):3–15. doi: 10.1016/0090-6980(77)90037-5. [DOI] [PubMed] [Google Scholar]
  5. Ellis E. F., Oelz O., Roberts L. J., 2nd, Payne N. A., Sweetman B. J., Nies A. S., Oates J. A. Coronary arterial smooth muscle contraction by a substance released from platelets: evidence that it is thromboxane A2. Science. 1976 Sep 17;193(4258):1135–1137. doi: 10.1126/science.959827. [DOI] [PubMed] [Google Scholar]
  6. Fried J., Barton J. Synthesis of 13,14-dehydroprostacyclin methyl ester: a potent inhibitor of platelet aggregation. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2199–2203. doi: 10.1073/pnas.74.6.2199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gryglewski R. J., Bunting S., Moncada S., Flower R. J., Vane J. R. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins. 1976 Nov;12(5):685–713. doi: 10.1016/0090-6980(76)90047-2. [DOI] [PubMed] [Google Scholar]
  8. Hamberg M., Samuelsson B. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A. 1973 Mar;70(3):899–903. doi: 10.1073/pnas.70.3.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung. Biochem Biophys Res Commun. 1974 Dec 11;61(3):942–949. doi: 10.1016/0006-291x(74)90246-0. [DOI] [PubMed] [Google Scholar]
  10. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamberg M., Svensson J., Wakabayashi T., Samuelsson B. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci U S A. 1974 Feb;71(2):345–349. doi: 10.1073/pnas.71.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hintze T. H., Kaley G. Prostaglandins and the control of blood flow in the canine myocardium. Circ Res. 1977 Mar;40(3):313–320. doi: 10.1161/01.res.40.3.313. [DOI] [PubMed] [Google Scholar]
  13. Hyman A. L., Chapnick B. M., Kadowitz P. J., Lands W. E., Crawford C. G., Fried J., Barton J. Unusual pulmonary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with endoperoxides and other prostanoids. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5711–5715. doi: 10.1073/pnas.74.12.5711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kadowitz P. J., Hyman A. L. Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed. Circ Res. 1977 Mar;40(3):282–287. doi: 10.1161/01.res.40.3.282. [DOI] [PubMed] [Google Scholar]
  15. Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
  16. Needleman P., Moncada S., Bunting S., Vane J. R., Hamberg M., Samuelsson B. Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature. 1976 Jun 17;261(5561):558–560. doi: 10.1038/261558a0. [DOI] [PubMed] [Google Scholar]
  17. Nugteren D. H., Hazelhof E. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim Biophys Acta. 1973 Dec 20;326(3):448–461. doi: 10.1016/0005-2760(73)90145-8. [DOI] [PubMed] [Google Scholar]
  18. Pace-Asciak C. Polyhydroxy cyclic ethers formed from tritiated arachidonic acid by acetone powders of sheep seminal vesicles. Biochemistry. 1971 Sep 28;10(20):3664–3669. doi: 10.1021/bi00796a005. [DOI] [PubMed] [Google Scholar]
  19. Pace-Asciak C., Wolfe L. S. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry. 1971 Sep 28;10(20):3657–3664. doi: 10.1021/bi00796a004. [DOI] [PubMed] [Google Scholar]
  20. Paustian P. W., Chapnick B. M., Feigen L. P., Hyman A. L., Kadowitz P. J. Effects of 13, 14-dehydroprostacyclin methyl ester on the feline intestinal vascular bed. Prostaglandins. 1977;14(6):1141–1152. doi: 10.1016/0090-6980(77)90291-x. [DOI] [PubMed] [Google Scholar]
  21. Svensson J., Hamberg M. Thromboxane A2 and prostaglandin H2: potent stimulators of the swine coronary artery. Prostaglandins. 1976 Dec;12(6):943–950. doi: 10.1016/0090-6980(76)90128-3. [DOI] [PubMed] [Google Scholar]
  22. Whittaker N., Bunting S., Salmon J., Moncada S., Vane J. R., Johnson R. A., Morton D. R., Kinner J. H., Gorman R. R., McGuire J. C. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins. 1976 Dec;12(6):915–928. doi: 10.1016/0090-6980(76)90126-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES