WB4101-SENSITIVE AND CEC-SENSITIVE POSITIVE INOTROPIC ACTIONS OF PHENYLEPHRINE IN RAT CARDIAC-MUSCLE

This study was designed to determine the role of the alpha(1)-adrenerg ic receptor (AR) subtypes in the positive inotropic action of alpha(1) -adrenergic agonists in rat myocardium. Isolated left atrial and papil lary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 de grees C) containing 3 mu M nadolol and paced at 3.3 Hz. Isometric tens ion was continuously monitored. Cumulative concentration-response curv es 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 tre atment with chloroethylclonidine (CEC; 10, 100, and 300 mu M). WB4101 antagonized the effect of phenylephrine in both tissues, increasing ha lf-maximal effective concentration (EC(50)) values in a concentration- dependent manner. CEC pretreatment also increased EC(50) values in bot h tissues, and 300 mu M CEC reduced the maximal positive inotropic eff ect of phenylephrine by similar to 48 and 38% in left atrial and papil lary muscle, respectively. CEC alone elicited significant increases in contractile force that were not readily reversible. These data sugges t that the positive inotropic effect of alpha(1)-adrenergic agonists i n rat atrial and ventricular myocardium results from stimulation of bo th WB4101- and CEC-sensitive alpha(1)-ARS.