Use of hexobendine to examine whether the coronary vasodilator metabolite released from guinea-pig isolated hearts is adenosine.
The coronary vasodilatation that accompanies cardiac stimulation by catecholamines and histamine or exposure to hypoxia is thought to be due to the release of a coronary vasodilator metabolite. Adenosine has been proposed as a likely candidate and this study examines its possible involvement by use of hexobendine, an agent that enhances the effects of adenosine. The force and rate of contraction and coronary perfusion pressure of isolated guinea-pig hearts were recorded. Adenosine exerted dose-dependent negative chronotropic effects and coronary vasodilatation. Both responses were potentiated during perfusion with hexobendine. However, hexobendine did not potentiate the coronary vasodilator responses to isoprenaline, suggesting that adenosine was not involved. Isolated hearts were then perfused in series, the donor heart supplying perfusate to the recipient. Stimulation of donor hearts by isoprenaline or histamine resulted in coronary vasodilator activity appearing in the recipient, which had received the appropriate antagonists of beta-adrenoceptors of histamine H1- and H2-receptors. Exposure of donor hearts to hypoxia also caused vasodilator metabolite release. Infusion of hexobendine into the recipient heats potentiated the vasodilator metabolite release. Infusion of hexobendine into the recipient hearts potentiated the vasodilator responses to exogenous adenosine, however, the responses to vasodilator metabolite released by the three procedures was not affected. Furthermore, there were no negative chronotropic responses accompanying the vasodilator metabolite release as there were with adenosine in a dose that produced equivalent vasodilatation. These results provide evidence that the vasoactive metabolite released by catecholamines, histamine and hypoxia is not adenosine.
D000241:Adenosine / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006592:Hexobendine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
D001565:Benzoates; D006632:Histamine; D006592:Hexobendine; D000241:Adenosine; D007545:Isoproterenol; D010100:Oxygen