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.
Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
S L
SL
Buzzard
E
E
Seifen
J P
JP
Lindemann
R H
RH
Kennedy
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013268:Stimulation, Chemical
D000316:Adrenergic alpha-Agonists; D001639:Bicarbonates; D002712:Chlorides; D017923:Sodium-Hydrogen Exchangers; D010656:Phenylephrine; D007545:Isoproterenol; D002118:Calcium