EFFECTS OF WB4101 AND CHLOROETHYLCLONIDINE ON THE POSITIVE AND NEGATIVE INOTROPIC ACTIONS OF PHENYLEPHRINE IN RAT CARDIAC-MUSCLE

This study was designed to determine if the positive and negative inot ropic actions of alpha-1-adrenergic agonists in rat atrial and ventric ular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in is olated left atrial and papillary muscle before and after treatment wit h prazosin, WB4101 ethyl]-2,3-dihydro-1,4-benzodioxin-2-methanamine}, chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 mu M ) elicited a monophasic positive inotropic response in left atrial mus cle and a triphasic inotropic action in papillary muscle (transient po sitive, then negative inotropic components preceding a sustained posit ive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagon ized the transient negative inotropic component in papillary muscle. T he transient positive inotropic response was not affected by CEC, WB41 01 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic ef fect of alpha-1-adrenergic agonists in rat atrial and ventricular myoc ardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response i n ventricular preparations is mediated via alpha-1B ARs. However, pres ent data do not exclude the possibility that the CEC-sensitive inotrop ic responses elicited by phenylephrine may be mediated in part by othe r recently described alpha-1 subtypes. The receptors involved in the t ransient positive inotropic action cannot be identified by current res ults.