Alpha 1-adrenoceptors in neonatal rat cardiac myocytes: hypoxia alters the responsiveness of alpha 1A and alpha 1B subtypes.

We investigated the contribution of alpha 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 alpha 1A- and alpha 1B-adrenoceptor subtypes as measured by [3H]prazosin binding following CEC treatment. These results indicate (1) that cultured neonatal rat cardiac myocytes contain both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, and (2) that the predominant alpha 1-adrenoceptor subtypes mediating NE-induced chronotropy were altered by hypoxia.