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. 1982 Feb;75(2):269–286. doi: 10.1111/j.1476-5381.1982.tb08783.x

Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat.

S E Belo, J Talesnik
PMCID: PMC2071609  PMID: 6764740

Abstract

The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator. The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5 mg/l) and naproxen (12.5-25 mg/1) reversibly inhibited both phases of the response induced by AA. Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. Short infusions of acetylsalicylic acid at low concentrations (2.9 micrograms/ml), dipyridamole (0.6 micrograms/ml) and sulphinpyrazone (28.7 micrograms/ml) selectively inhibited the vasoconstrictor phase of the response to AA. It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. Linolenic, linoleic, dihomo-gamma-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.

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Selected References

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  1. Ahumada G. G., Sobel B. E., Needleman P. Synthesis of prostaglandins by cultured rat hearts myocytes and cardiac mesenchymal cells. J Mol Cell Cardiol. 1980 Jul;12(7):685–700. doi: 10.1016/0022-2828(80)90099-1. [DOI] [PubMed] [Google Scholar]
  2. Al-Ubaidi F., Bakhle Y. S. Differences in biological activation of arachidonic acid in perfused lungs from guinea pig, rat and man. Eur J Pharmacol. 1980 Mar 7;62(1):89–96. doi: 10.1016/0014-2999(80)90484-7. [DOI] [PubMed] [Google Scholar]
  3. Ali A. E., Barrett J. C., Eling T. E. Prostaglandin and thromboxane production by fibroblasts and vascular endothelial cells. Prostaglandins. 1980 Oct;20(4):667–688. doi: 10.1016/0090-6980(80)90107-0. [DOI] [PubMed] [Google Scholar]
  4. Ali M., McDonald J. W. Effects of sulfinpyrazone on platelet prostaglandin synthesis and platelet release of serotonin. J Lab Clin Med. 1977 Apr;89(4):868–875. [PubMed] [Google Scholar]
  5. Ally A. I., Manku M. S., Horrobin D. F., Morgan R. O., Karmazin M., Karmali R. A. Dipyridamole: a possible potent inhibitor of thromboxane A2 synthetase in vascular smooth muscle. Prostaglandins. 1977 Sep;14(3):607–609. doi: 10.1016/0090-6980(77)90278-7. [DOI] [PubMed] [Google Scholar]
  6. Anhut H., Bernauer W., Peskar B. A. Pharmacological modification of thromboxane and prostaglandin release in cardiac anaphylaxis. Prostaglandins. 1978 May;15(5):889–900. doi: 10.1016/0090-6980(78)90156-9. [DOI] [PubMed] [Google Scholar]
  7. Anhut H., Bernauer W., Peskar B. A. Radioimmunological determination of thromboxane release in cardiac anaphylaxis. Eur J Pharmacol. 1977 Jul 1;44(1):85–88. doi: 10.1016/0014-2999(77)90120-0. [DOI] [PubMed] [Google Scholar]
  8. BLEEHEN N. M., FISHER R. B. The action of insulin in the isolated rat heart. J Physiol. 1954 Feb 26;123(2):260–276. doi: 10.1113/jphysiol.1954.sp005049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bourgain R. H., Andries R., Finne E. The role of prostaglandins in platelet-vessel wall interaction. Arch Int Pharmacodyn Ther. 1979 May;239(1):161–163. [PubMed] [Google Scholar]
  10. Braunwald E. Coronary spasm and acute myocardial infarction--new possibility for treatment and prevention. N Engl J Med. 1978 Dec 7;299(23):1301–1303. doi: 10.1056/NEJM197812072992309. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Burch J. W., Stanford N., Majerus P. W. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest. 1978 Feb;61(2):314–319. doi: 10.1172/JCI108941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Carlson T. H., Wentland S. H., Leonard B. D., Ruder M. A., Reeve E. B. Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level. Am J Physiol. 1978 Aug;235(2):H223–H230. doi: 10.1152/ajpheart.1978.235.2.H223. [DOI] [PubMed] [Google Scholar]
  14. De Deckere E. A. Effects of prostaglandins on coronary flow rate and left ventricular work in isolated rat heart. Eur J Pharmacol. 1979 Sep 15;58(2):211–213. doi: 10.1016/0014-2999(79)90015-3. [DOI] [PubMed] [Google Scholar]
  15. Drake A. J., Haines J. R., Noble M. I. Preferential uptake of lactate by the normal myocardium in dogs. Cardiovasc Res. 1980 Feb;14(2):65–72. doi: 10.1093/cvr/14.2.65. [DOI] [PubMed] [Google Scholar]
  16. Dusting G. J., Chapple D. J., Hughes R., Moncada S., Vane J. R. Prostacyclin (PGI2) induces coronary vasodilatation in anaesthetised dogs. Cardiovasc Res. 1978 Dec;12(12):720–730. [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Fallen E. L., Elliott W. C., Gorlin R. Apparatus for study of ventricular function and metabolism in the isolated perfused rat heart. J Appl Physiol. 1967 Apr;22(4):836–839. doi: 10.1152/jappl.1967.22.4.836. [DOI] [PubMed] [Google Scholar]
  20. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  21. Gerber J. G., Nies A. S. The hemodynamic effects of prostaglandins in the rat. Evidence for important species variation in renovascular responses. Circ Res. 1979 Mar;44(3):406–410. doi: 10.1161/01.res.44.3.406. [DOI] [PubMed] [Google Scholar]
  22. Gordon J. L., Pearson J. D. Effects of sulphinpyrazone and aspirin on prostaglandin I2 (prostacyclin) synthesis by endothelial cells. Br J Pharmacol. 1978 Dec;64(4):481–483. doi: 10.1111/j.1476-5381.1978.tb17308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gorman R. R. Modulation of human platelet function by prostacyclin and thromboxane A2. Fed Proc. 1979 Jan;38(1):83–88. [PubMed] [Google Scholar]
  24. Greenwald J. E., Wong L. K., Rao M., Bianchine J. R., Panganamala R. V. A study of three vasodilating agents as selective inhibitors of thromboxane A2 biosynthesis. Biochem Biophys Res Commun. 1978 Oct 30;84(4):1112–1118. doi: 10.1016/0006-291x(78)91698-4. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Gryglewski R., Vane J. R. The release of prostaglandins and rabbit aorta contracting substance (RCS) from rabbit spleen and its antagonism by anti-inflammatory drugs. Br J Pharmacol. 1972 May;45(1):37–47. doi: 10.1111/j.1476-5381.1972.tb09574.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hamberg M., Svensson J., Hedqvist P., Strandberg K., Samuelsson B. Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Adv Prostaglandin Thromboxane Res. 1976;1:495–501. [PubMed] [Google Scholar]
  28. 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]
  29. Harlan D. M., Rooke T. W., Belloni F. L., Sparks H. V. Effect of indomethacin on coronary vascular response to increased myocardial oxygen consumption. Am J Physiol. 1978 Oct;235(4):H372–H378. doi: 10.1152/ajpheart.1978.235.4.H372. [DOI] [PubMed] [Google Scholar]
  30. Higgs G. A., Cardinal D. C., Moncada S., Vane J. R. Microcirculatory effects of prostacyclin (PGI2) in the hamster cheek pouch. Microvasc Res. 1979 Sep;18(2):245–254. doi: 10.1016/0026-2862(79)90032-3. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Hornstra G., Haddeman E., Don J. A. Blood platelets do not provide endoperoxides for vascular prostacyclin production. Nature. 1979 May 3;279(5708):66–68. doi: 10.1038/279066a0. [DOI] [PubMed] [Google Scholar]
  33. Hyman A. L., Kadowitz P. J., Lands W. E., Crawford C. G., Fried J., Barton J. Coronary vasodilator activity of 13,14-dehydroprostacyclin methyl ester: comparison with prostacyclin and other prostanoids. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3522–3526. doi: 10.1073/pnas.75.7.3522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Hyman A. L., Spannhake E. W., Kadowitz P. J. Divergent responses to arachidonic acid in the feline pulmonary vascular bed. Am J Physiol. 1980 Jul;239(1):H40–H46. doi: 10.1152/ajpheart.1980.239.1.H40. [DOI] [PubMed] [Google Scholar]
  35. Kadowitz P. J., Spannhake E. W., Greenberg S., Feigen L. P., Hyman A. Comparative effects of arachidonic acid, bisenoic prostaglandins, and an endoperoxide analog on the canine pulmonary vascular bed. Can J Physiol Pharmacol. 1977 Dec;55(6):1369–1377. doi: 10.1139/y77-182. [DOI] [PubMed] [Google Scholar]
  36. Kalsner S. Endogenous prostaglandin release contributes directly to coronary artery tone. Can J Physiol Pharmacol. 1975 Aug;53(4):560–565. doi: 10.1139/y75-079. [DOI] [PubMed] [Google Scholar]
  37. Kulkarni P. S., Roberts R., Needleman P. Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate. Prostaglandins. 1976 Sep;12(3):337–353. doi: 10.1016/0090-6980(76)90015-0. [DOI] [PubMed] [Google Scholar]
  38. Lands W. E. The biosynthesis and metabolism of prostaglandins. Annu Rev Physiol. 1979;41:633–652. doi: 10.1146/annurev.ph.41.030179.003221. [DOI] [PubMed] [Google Scholar]
  39. Lewy R. I., Wiener L., Walinsky P., Lefer A. M., Silver M. J., Smith J. B. Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature. Circulation. 1980 Jun;61(6):1165–1171. doi: 10.1161/01.cir.61.6.1165. [DOI] [PubMed] [Google Scholar]
  40. Limas C. J., Cohn J. N. Isolation and properties of myocardial prostaglandin synthetase. Cardiovasc Res. 1973 Sep;7(5):623–628. doi: 10.1093/cvr/7.5.623. [DOI] [PubMed] [Google Scholar]
  41. MacIntyre D. E., Pearson J. D., Gordon J. L. Localisation and stimulation of prostacyclin production in vascular cells. Nature. 1978 Feb 9;271(5645):549–551. doi: 10.1038/271549a0. [DOI] [PubMed] [Google Scholar]
  42. Maseri A., L'Abbate A., Chierchia S., Parodi O., Severi S., Biagini A., Distante A., Marzilli M., Ballerstra A. M. Significance of spasm in the pathogenesis of ischemic heart disease. Am J Cardiol. 1979 Oct 22;44(5):788–792. doi: 10.1016/0002-9149(79)90198-x. [DOI] [PubMed] [Google Scholar]
  43. Mentz P., Blass K. E., Förster W. Effects of prostaglandin precursors and other unsaturated fatty acids on coronary flow and cardiac action in vivo and in vitro. Acta Biol Med Ger. 1976;35(8-9):1159–1160. [PubMed] [Google Scholar]
  44. Mentz P., Forster W. The influence of unsaturated fatty acids on prostaglandin-release in isolated perfused guinea-pig hearts. Prostaglandins. 1977 Jul;14(1):173–179. doi: 10.1016/0090-6980(77)90166-6. [DOI] [PubMed] [Google Scholar]
  45. Messina E. J., Rodenburg J., Slomiany B. L., Roberts A. M., Hintze T. H., Kaley G. Microcirculatory effects of arachidonic acid and a prostaglandin endoperoxide (PGH2). Microvasc Res. 1980 May;19(3):288–296. doi: 10.1016/0026-2862(80)90049-7. [DOI] [PubMed] [Google Scholar]
  46. Minkes M. S., Douglas J. R., Jr, Needleman P. Prostaglandin release by the isolated perfused rabbit heart. Prostaglandins. 1973 Apr;3(4):439–445. doi: 10.1016/0090-6980(73)90151-2. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. Moncada S., Vane J. R. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin. Pharmacol Rev. 1978 Sep;30(3):293–331. [PubMed] [Google Scholar]
  49. Needleman P. Experimental criteria for evaluating prostaglandin biosynthesis and intrinsic function. Biochem Pharmacol. 1978;27(11):1515–1518. doi: 10.1016/0006-2952(78)90477-x. [DOI] [PubMed] [Google Scholar]
  50. Needleman P. The synthesis and function of prostaglandins in the heart. Fed Proc. 1976 Oct;35(12):2376–2381. [PubMed] [Google Scholar]
  51. Nugteren D. H., Jouvenaz G. H., Dutilh C. E. Determination of prostaglandins and other products of arachidonate oxygenation in perfusates and during platelet aggregation. Acta Biol Med Ger. 1978;37(5-6):701–706. [PubMed] [Google Scholar]
  52. Ogletree M. L., Smith J. B., Lefer A. M. Actions of prostaglandins on isolated perfused cat coronary arteries. Am J Physiol. 1978 Oct;235(4):H400–H406. doi: 10.1152/ajpheart.1978.235.4.H400. [DOI] [PubMed] [Google Scholar]
  53. Opie L. Effect of extracellular pH on function and metabolism of isolated perfused rat heart. Am J Physiol. 1965 Dec;209(6):1075–1080. doi: 10.1152/ajplegacy.1965.209.6.1075. [DOI] [PubMed] [Google Scholar]
  54. Owen T. L., Ehrhart I. C., Weidner W. J., Scott J. B., Haddy F. J. Effects of indomethacin on local blood flow regulation in canine heart and kidney. Proc Soc Exp Biol Med. 1975 Sep;149(4):871–876. doi: 10.3181/00379727-149-38916. [DOI] [PubMed] [Google Scholar]
  55. Parratt J. R., Marshall R. J. Are prostaglandins involved in the regulation of coronary blood flow? A review of the evidence. Acta Biol Med Ger. 1978;37(5-6):747–754. [PubMed] [Google Scholar]
  56. Rane A., Oelz O., Frolich J. C., Seyberth H. W., Sweetman B. J., Watson J. T., Wilkinson G. R., Oates J. A. Relation between plasma concentration of indomethacin and its effect on prostaglandin synthesis and platelet aggregation in man. Clin Pharmacol Ther. 1978 Jun;23(6):658–668. doi: 10.1002/cpt1978236658. [DOI] [PubMed] [Google Scholar]
  57. Raz A., Stern H., Kenig-Wakshal R. Indomethacin and aspirin inhibition of prostaglandin E2 synthesis by sheep seminal vesicles microsome powder. Prostaglandins. 1973 Mar;3(3):337–352. doi: 10.1016/0090-6980(73)90072-5. [DOI] [PubMed] [Google Scholar]
  58. Salzman P. M., Salmon J. A., Moncada S. Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery. J Pharmacol Exp Ther. 1980 Oct;215(1):240–247. [PubMed] [Google Scholar]
  59. Samuelsson B. Prostaglandin endoperoxides and thromboxanes: role in platelets and in vascular and respiratory smooth muscle. Acta Biol Med Ger. 1976;35(8-9):1055–1063. [PubMed] [Google Scholar]
  60. Samuelsson B., Wennmalm A. Increased nerve stimulation induced release of noradrenaline from the rabbit heart after inhibition of prostaglandin synthesis. Acta Physiol Scand. 1971 Oct;83(2):163–168. doi: 10.1111/j.1748-1716.1971.tb05065.x. [DOI] [PubMed] [Google Scholar]
  61. Schaper W., Schaper J. The coronary microcirculation. Am J Cardiol. 1977 Dec;40(6):1008–1012. doi: 10.1016/0002-9149(77)90053-4. [DOI] [PubMed] [Google Scholar]
  62. Schrör K., Link H. B., Rösen R., Klaus W., Rösen P. Prostacyclin-induced coronary vasodilation. Interactions with adenosine, cyclic AMP and energy charge in the rat heart in vitro. Eur J Pharmacol. 1980 Jun 27;64(4):341–348. doi: 10.1016/0014-2999(80)90242-3. [DOI] [PubMed] [Google Scholar]
  63. Schrör K., Moncada S., Ubatuba F. B., Vane J. R. Transformation of arachidonic acid and prostaglandin endoperoxides by the guinea pig heart. Formation of RCS and prostacyclin. Eur J Pharmacol. 1978 Jan 1;47(1):103–114. doi: 10.1016/0014-2999(78)90380-1. [DOI] [PubMed] [Google Scholar]
  64. Schrör K., Sauerland S., Kuhn A., Rösen R. Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs. Naunyn Schmiedebergs Arch Pharmacol. 1980 Aug;313(1):69–76. doi: 10.1007/BF00505806. [DOI] [PubMed] [Google Scholar]
  65. Sen A. K., Sunahara F. A., Talesnik J. Coronary reactions to cardiac hyperactivity and to hypoxia in isolated perfused heart of rat. Br J Pharmacol. 1977 Nov;61(3):381–393. doi: 10.1111/j.1476-5381.1977.tb08430.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Sen A. K., Sunahara F. A., Talesnik J. Prostaglandin E2 and cyclic AMP in the coronary vasodilatation due to cardiac hyperactivity. Can J Physiol Pharmacol. 1976 Apr;54(2):128–139. doi: 10.1139/y76-021. [DOI] [PubMed] [Google Scholar]
  67. Silberbauer K., Sinzinger H., Winter M., Feigl W., Ring F. Prostacyclin-like activity of endothelium and subendothelium - important for atherosclerosis? Experientia. 1978 Nov 15;34(11):1471–1472. doi: 10.1007/BF01932360. [DOI] [PubMed] [Google Scholar]
  68. Sivakoff M., Pure E., Hsueh W., Needleman P. Prostaglandins and the heart. Fed Proc. 1979 Jan;38(1):78–82. [PubMed] [Google Scholar]
  69. Smith W. L., Lands W. E. Stimulation and blockade of prostaglandin biosynthesis. J Biol Chem. 1971 Nov;246(21):6700–6702. [PubMed] [Google Scholar]
  70. Srivastava K. C. Arachidonic acid as a precursor in the production of substances necessary for platelet aggregation and its control. Dan Med Bull. 1978 Apr;25(3):130–133. [PubMed] [Google Scholar]
  71. Sunahara F. A., Talesnik J. Myocardial synthesis of prostaglandin-like substances and coronary reactions to cardiostimulation and to hypoxia. Br J Pharmacol. 1979 Jan;65(1):71–85. doi: 10.1111/j.1476-5381.1979.tb17335.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Terashita Z. I., Fukui H., Nishikawa K., Hirata M., Kikuchi S. Coronary vasospastic action of thromboxane A2 in isolated, working guinea pig hearts. Eur J Pharmacol. 1978 Dec 15;53(1):49–56. doi: 10.1016/0014-2999(78)90266-2. [DOI] [PubMed] [Google Scholar]
  73. Tuvemo T., Strandberg K., Hamberg M., Samuelsson B. Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery. Acta Physiol Scand. 1976 Feb;96(2):145–149. doi: 10.1111/j.1748-1716.1976.tb10183.x. [DOI] [PubMed] [Google Scholar]
  74. Vapaatalo H., Parantainen J., Metsä-Ketelä T., Kangasaho M. Prostaglandins and cyclic nucleotides in cardiac function. Pol J Pharmacol Pharm. 1978 Mar-Jun;30(2-3):195–213. [PubMed] [Google Scholar]
  75. Weissler A. M., Altschuld R. A., Gibb L. E., Pollack M. E., Kruger F. A. Effect of insulin on the performance and metabolism of the anoxic isolated perfused rat heart. Circ Res. 1973 Jan;32(1):108–116. doi: 10.1161/01.res.32.1.108. [DOI] [PubMed] [Google Scholar]
  76. Weksler B. B., Ley C. W., Jaffe E. A. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A 23187. J Clin Invest. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Weksler B. B., Marcus A. J., Jaffe E. A. Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3922–3926. doi: 10.1073/pnas.74.9.3922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wennmalm A. Prostacyclin-dependent coronary vasodilation in rabbit and guinea pig hearts. Acta Physiol Scand. 1979 May;106(1):47–52. doi: 10.1111/j.1748-1716.1979.tb06368.x. [DOI] [PubMed] [Google Scholar]
  79. 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]
  80. Wicks T. C., Rose J. C., Johnson M., Ramwell P. W., Kot P. A. Vascular responses to arachidonic acid in the perfused canine lung. Circ Res. 1976 Mar;38(3):167–171. doi: 10.1161/01.res.38.3.167. [DOI] [PubMed] [Google Scholar]
  81. ZACHARIAH P. Contractility and sugar permeability in the perfused rat heart. J Physiol. 1961 Sep;158:59–72. doi: 10.1113/jphysiol.1961.sp006754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. de Deckere E. A., Nugteren D. H., Ten Hoor F. Prostacyclin is the major prostaglandin released from the isolated perfused rabbit and rat heart. Nature. 1977 Jul 14;268(5616):160–163. doi: 10.1038/268160a0. [DOI] [PubMed] [Google Scholar]
  83. de Kock A., Lochner A., Kotzé J. C., Gevers W. The hypoxic, low-flow perfused rat heart: characterization as a model of global ischaemia. Basic Res Cardiol. 1978 Sep-Oct;73(5):506–522. doi: 10.1007/BF01906530. [DOI] [PubMed] [Google Scholar]

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