WB4101- and CEC-sensitive positive inotropic actions of phenylephrine in rat cardiac muscle.
This study was designed to determine the role of the alpha 1-adrenergic receptor (AR) subtypes in the positive inotropic action of alpha 1-adrenergic agonists in rat myocardium. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 3 microM nadolol and paced at 3.3 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine (3 x 10(-7) to 3 x 10(-4) M) were obtained in the presence and absence of WB4101 (4 and 10 nM) and with and without treatment with chloroethylclonidine (CEC; 10, 100, and 300 microM). WB4101 antagonized the effect of phenylephrine in both tissues, increasing half-maximal effective concentration (EC50) values in a concentration-dependent manner. CEC pretreatment also increased EC50 values in both tissues, and 300 microM CEC reduced the maximal positive inotropic effect of phenylephrine by approximately 48 and 38% in left atrial and papillary muscle, respectively. CEC alone elicited significant increases in contractile force that were not readily reversible. These data suggest that the positive inotropic effect of alpha 1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of both WB4101- and CEC-sensitive alpha 1-ARs.
Williamson
A P
AP
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Seifen
E
E
Lindemann
J P
JP
Kennedy
R H
RH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010656:Phenylephrine; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine