Implications of altered inotropic effects of phenylephrine in pressure-overloaded cat ventricular muscle.
The positive inotropic action of phenylephrine in cardiac muscle is mediated by alpha- and beta-adrenoceptors. Data suggest the responsiveness of myocardium to inotropic agents is altered in cardiac disease. We evaluated the actions of phenylephrine on isometric contraction and K+-induced contracture in isolated cat right ventricular muscle from normal hearts and hearts with partial pulmonary artery ligation-induced pressure overload of 5-11 days in duration. Peak contractile force (Po) and rate of force development (dP/dt) were lower (p less than or equal to 0.005) in pressure-overloaded (0.59 +/- 0.2 g/mm2 and 4.6 +/- 1.7 g/s/mm2, respectively) than in normal (1.33 +/- 0.2 g/mm2 and 10.5 +/- 1.6 g/s/mm2, respectively) muscle. Phenylephrine (10(-6), 5 X 10(-6), and 10(-5) M) significantly (p less than or equal to 0.01) increased Po and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 X 10(-6) M) reduced peak K+-induced contracture force (Pc) similarly in normal (-30 +/- 8%) and pressure-overloaded (-36 +/- 11%) muscles. beta-Adrenergic blockade (nadolol, 10(-4) M) reduced, but did not abolish, the "relaxant" action of the drug on Pc in both muscle groups. The lack of a positive inotropic effect of phenylephrine in pressure-overloaded muscle suggests a derangement in both alpha- and beta-adrenoceptor function in this model of cardiac disease.
D000818:Animals; D001794:Blood Pressure; D002415:Cats; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects
D011941:Receptors, Adrenergic; D010656:Phenylephrine; D000242:Cyclic AMP; D011188:Potassium