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 α- and β-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 (P₀) and rate of force development (dP/dt) were lower (p ≤ 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 ≤ 0.01) increased P₀ and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 x 10^-6 M) reduced peak K⁺-induced contracture force (P(c)) similarly in normal (-30 ± 8%) and pressure-overloaded (-36 ± 11%) muscles. β-Adrenergic blockade (nadolol, 10^-4 M) reduced, but did not abolish, the 'relaxant' action of the drug on P(c) in both muscle groups. The lack of a positive inotropic effect of phenylephrine in pressure-overloaded muscle suggests a derangement in both α- and β-adrenoceptor function in this model of cardiac disease.