Abstract
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 (Po) and rate of force development (dP/dt) were lower (p ≥ 0.005) in pressure-overloaded (0.59 ± 0.2 g/mm and 4.6 ± 1.7 g/s/mm, respectively) than in normal (1.33 ± 0.2 g/mm and 10.5 ± 1.6 g/s/mm, respectively) muscle. Phenylephrine (10, 5 × 10, and 10M) significantly (p ≥ 0.01) increased Po and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 × 10M) reduced peak K -induced contracture force (Pc) similarly in normal (-30 ± 8%) and pressure-overloaded (-36 ± 11%) muscles. β-Adrenergic blockade (nadolol, 10M) 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 α- and β-adrenoceptor function in this model of cardiac disease.
