Altered coronary and cardiac adrenergic response in the failing hamster heart: role of cyclooxygenase derivatives.
Although the influence of the adrenergic system has been studied in the presence of heart failure, controversies still exist. Since cyclooxygenase derivatives appear to modulate coronary and cardiac adaptation in the failing heart, we hypothesized that cyclooxygenase derivatives may participate in the altered adrenergic responses in this situation. Isolated hearts from cardiomyopathic (UM-X7.1 subline) and normal hamsters, aged > 240 days, were utilized. Coronary and cardiac response to alpha1-, beta1-, and beta2-adrenergic stimulations was observed before and after pretreatment with indomethacin, a cyclooxygenase inhibitor. Reduction of coronary flow elicited by alpha1-adrenergic stimulation was unchanged in the presence of heart failure, while beta1- and beta2-induced vasodilatations were reduced. Inotropic response to alpha1 and beta1 stimulations were also reduced in failing hearts, while beta2-adrenergic action was unchanged. Pretreatment with indomethacin exacerbated coronary flow reduction observed with alpha1 stimulation in failing hearts only. Beta2-induced coronary vasodilatation and inotropic response to alpha1 and beta2 stimulations were impaired similarly in the presence of indomethacin in normal and failing hearts. The results suggest a complex interaction between adrenergic and cyclooxygenase activation.
Brousseau
Danica
D
Département de pharmacologie, Faculté de médecine, Université de Montreal, Succursale Centre-ville, QC, Canada.
Desjardins
Jean-François
JF
Jasmin
Gaëtan
G
Dumont
Louis
L
D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D006331:Heart Diseases / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D016861:Cyclooxygenase Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D010656:Phenylephrine; D004280:Dobutamine; D013726:Terbutaline; D007213:Indomethacin