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

This study was designed to determine if the sustained positive inotropic action of alpha-adrenergic stimulation is affected by the absence of extracellular chloride ion (Clo-). Atrial and papillary muscle were isolated from adult male rats, bathed in Krebs-Henseleit solution (30 degrees 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 Ca2+. The dose-dependent positive inotropic effects of isoproterenol and Ca2+ were not altered by the absence of Clo-. 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 Clo- to 0.39 +/- 0.06 g in the absence of Clo-; control developed tension was 0.60 +/- 0.08 and 0.47 +/- 0.10 g in these two groups before exposure to the alpha-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 Clo-, respectively; and the maximum inotropic responses to phenylephrine were 0.71 +/- 0.12 and 0.27 +/- 0.13 g. EC50 values for phenylephrine were not significantly affected by substitution for Cl-. Similar results were observed in a Hepes-buffered bathing solution without bicarbonate (HCO3-). These results indicate that the positive inotropic action of alpha-adrenergic stimulation is mediated in part by a mechanism requiring Cl-. Furthermore, data suggest that the antagonistic effect of Clo- removal is not mediated via Cl-/HCO3- exchange.