EFFECTS OF EXTRACELLULAR CL- ON THE INOTROPIC RESPONSE TO ALPHA-ADRENOCEPTOR STIMULATION

This study was designed to determine if the sustained positive inotrop ic action of alpha-adrenergic stimulation is affected by the absence o f extracellular chloride ion (Cl-0(-)). Atrial and papillary muscle we re isolated from adult male rats, bathed in Krebs-Henseleit solution ( 30 degrees C) with and without Cl- (methane-sulfonate substitution), a nd stimulated at 0.5 Hz. Isometric developed tension was monitored dur ing cumulative addition of phenylephrine, isoproterenol and Ca2+. The dose-dependent positive inotropic effects of isoproterenol and Ca2+ we re not altered by the absence of Cl-0(-). However, the magnitude of th e response to phenylephrine was diminished in both tissues. In atrial muscle, the maximum positive inotropic effect of phenylephrine was red uced from 2.05 +/- 0.17 g in the presence of Cl-0(-) to 0.39 +/- 0.06 g in the absence of Cl-0(-); control developed tension was 0.60 +/- 0. 08 and 0.47 +/- 0.10 g in these two groups before exposure to the alph a-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-0(-), respectively; and the maximum inotropic responses to phenylep hrine were 0.71 +/- 0.12 and 0.27 +/- 0.13 g. EC(50) values for phenyl ephrine were not significantly affected by substitution for Cl-. Simil ar results were observed in a Hepes-buffered bathing solution without bicarbonate (HCO3-). These results indicate that the positive inotropi c action of alpha-adrenergic stimulation is mediated in part by a mech anism requiring Cl-. Furthermore, data suggest that the antagonistic e ffect of Cl-0(-) removal is not mediated via Cl-/HCO3- exchange.