The coronary vasodilator mediator released by hypoxia and isoprenaline is not affected by cyclo-oxygenase inhibition.
Donor and recipient guinea-pig hearts were perfused in series, the recipient being perfused with regassed donor effluent. Coronary perfusion pressure and force and rate of contraction were measured. Exposure of donor hearts to hypoxia (1.5 min) and to isoprenaline (5 ng) caused the appearance of vasodilator material in recipient hearts, the direct beta-adrenoceptor effects of isoprenaline carried over in the effluent being antagonized in the recipient by propranolol. Cyclo-oxygenase was inhibited by infusion of meclofenamate (60 micrograms X min-1) which consistently abolished the vasodilator responses to arachidonic acid added to the donor. The vasodilator responses of the donor to hypoxia and isoprenaline were unaffected by meclofenamate. The falls in perfusion pressure of the recipient in response to material released by these procedures were also not significantly different before (hypoxia, 11.5 +/- 2.6mm Hg; isoprenaline, 10.3 +/- 1.3mm Hg) and during the infusion (hypoxia, 10.2 +/- 4.1; isoprenaline, 11.0 +/- 1.3mm Hg). The coronary vasodilator responses to hypoxia and isoprenaline and the vasodilator material released by these procedures do not therefore appear to be due to products of arachidonic acid via cyclo-oxygenase pathways. Furthermore, since there was also no potentiation of the responses, there does not appear to be a concomitant release of a prostanoid to inhibit the major vasodilator material. Adenosine, as the likely candidate for this predominant vasodilator mediator, is discussed.
Broadley
K J
KJ
Rothaul
A L
AL
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016027:Heart Transplantation; D000860:Hypoxia / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D001095:Arachidonic Acids; D062367:ortho-Aminobenzoates; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; D011433:Propranolol; D007545:Isoproterenol