Effects of extracellular Cl − on the inotropic response to α-adrenoceptor stimulation

Abstract

This study was designed to determine if the sustained positive inotropic action of α-adrenergic stimulation is affected by the absence of extracellular chloride ion (Cl o −). Atrial and papillary muscle were isolated from adult male rats, bathed in Krebs-Henseleit solution (30°C) with and without Cl − (methane-sulfonate substitution), and stimulated at 0.5 Hz. Isometric developed tension was monitored during cumulative addition of phenylephrine, isoproterenol and Ca 2+. The dose-dependent positive inotropic effects of isoproterenol and Ca 2+ were not altered by the absence of Cl o −. However, the magnitude of the response to phenylephrine was diminished in both tissues. In atrial muscle, the maximum positive inotropic effect of phenylephrine was reduced from 2.05±0.17 g in the presence of Cl o − to 0.39±0.06 g in the absence of Cl o −; control developed tension was 0.60±0.08 and 0.47±0.10 g in these two groups before exposure to the α-adrenoceptor agonist. In papillary muscle, control developed tension was 1.40±0.11 and 1.17±0.18 g in the presence and absence of Cl o −, respectively; and the maximum inotropic responses to phenylephrine were 0.71±0.12 and 0.27±0.13 g. EC 50 values for phenylephrine were not significantly affected by substitution for Cl −. Similar results were observed in a Hepes-buffered bathing solution without bicarbonate (HCO 3 −). These results indicate that the positive inotropic action of α-adrenergic stimulation is mediated in part by a mechanism requiring Cl −. Furthermore, data suggest that the antagonistic effect of Cl o − removal is not mediated via Cl −/HCO 3 − exchange.