ONTOGENIC DIFFERENCES IN THE FUNCTIONS OF MYOCARDIAL ALPHA(1) ADRENOCEPTOR SUBTYPES IN RATS

The present study was done to determine possible ontogenic differences in the functions of rat myocardial alpha(1) adrenoceptor (alpha(1) AR ) subtypes in view of reported greater inotropic responses of myocardi um of neonatal than of adult rats to alpha(1) AR agonists. Methoxamine , phenylephrine and norepinephrine were used as alpha(1) AR agonists. Phenylephrine and norepinephrine were used in the presence of 3 mu M p ropranolol. It was found that the ratios of chloroethylclonidine (CEC) -insensitive alpha(1) AR subtype (alpha(1A) AR) to CEC-sensitive alpha (1) AR subtype (alpha(1B) AR) were approximately 50:50 in neonatal (1 week old) and 20:80 in adult rat ventricles. alpha(1A) AR selective an tagonists WE 4101 and 5-methylurapidil (5-MU) inhibited the inotropic effects of alpha(1) AR agonists both on neonatal and on adult rat vent ricles; in contrast, selective inactivation of alpha(1B) AR by CEC inh ibited the inotropic effects of alpha(1) AR agonists only on ventricle s from adult but not from neonatal animals. WE 4101 inhibited methoxam ine-induced increases in inositol phosphates by ventricular slices fro m both adult and neonatal rats; in contrast, CEC inhibited these effec ts of methoxamine only in tissues from adult but not in tissues from n eonatal animals. In conclusion, this study, to our knowledge, demonstr ates for the first time that the effects of alpha AR agonists on right ventricular contractions and phosphoinositol turnover are mediated pr imarily by alpha(1A) AR subtype in the neonatal and by both alpha(1A) AR and alpha(1B) AR subtypes in the adult rat.