Altered coronary and cardiac adrenergic response in the failing hamster heart: role of cyclooxygenase derivatives

Abstract

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 α1-, β1-, and β2-adrenergic stimulations was observed before and after pretreatment with indomethacin, a cyclooxygenase inhibitor. Reduction of coronary flow elicited by α1-adrenergic stimulation was unchanged in the presence of heart failure, while β1- and β2-induced vasodilatations were reduced. Inotropic response to α1 and β1 stimulations were also reduced in failing hearts, while β2-adrenergic action was unchanged. Pretreatment with indomethacin exacerbated coronary flow reduction observed with α1 stimulation in failing hearts only. β2-induced coronary vasodilatation and inotropic response to α1 and β2 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.Key words: adrenergic, cyclooxygenase, heart failure, coronary flow, cardiac dynamics.