α1-adrenoceptors in neonatal rat cardiac myocytes: Hypoxia alters the responsiveness of α1A and α1B subtypes

Abstract

We investigated the contribution of α 1-adrenoceptor subtypes to the chronotropic response to norepinephrine (NE) in cultured neonatal rat cardiac myocytes under normoxia and hypoxia. A dose-dependent negative chronotropic response was induced by NE in the presence of propranolol. Hypoxic exposure inverted the negative chronotropic response to NE to a positive one. All of these chronotropic responses were completely antagonized by prazosin. In normoxic conditions, the NE-induced negative chronotropic response was completely antagonized by WB4101 but only partially (55%) so by chloroethylclonidine (CEC). After hypoxic exposure, WB4101 partially antagonized the positive chronotropic response to NE (54%), while CEC completely suppressed the action of NE. Hypoxic exposure did not alter the number of α 1A - and α 1B-adrenoceptor subtypes as measured by [ 3H]prazosin binding following CEC treatment. These results indicate (1) that cultured neonatal rat cardiac myocytes contain both α 1-adrenoceptor subtypes, i.e., α 1A and α 1B, and (2) that the predominant α 1-adrenoceptor subtypes mediating NE-induced chronotropy were altered by hypoxia.