ALPHA(1)-ADRENOCEPTORS IN NEONATAL RAT CARDIAC MYOCYTES - HYPOXIA ALTERS THE RESPONSIVENESS OF ALPHA(1A) AND ALPHA(1B) SUBTYPES

We investigated the contribution of alpha1-adrenoceptor subtypes to th e chronotropic response to norepinephrine (NE) in cultured neonatal ra t cardiac myocytes under normoxia and hypoxia. A dose-dependent negati ve chronotropic response was induced by NE in the presence of proprano lol. Hypoxic exposure inverted the negative chronotropic response to N E to a positive one. All of these chronotropic responses were complete ly antagonized by prazosin. In normoxic conditions, the NE-induced neg ative chronotropic response was completely antagonized by WB4101 but o nly partially (55%) so by chloroethylclonidine (CEC). After hypoxic ex posure, WB4101 partially antagonized the positive chronotropic respons e to NE (54%), while CEC completely suppressed the action of NE. Hypox ic exposure did not alter the number of alpha1A- and alpha1B-adrenocep tor subtypes as measured by [H-3]prazosin binding following CEC treatm ent. These results indicate (1) that cultured neonatal rat cardiac myo cytes contain both alpha1-adrenoceptor subtypes, i.e., alpha1A and alp ha1B and (2) that the predominant alpha1-adrenoceptor subtypes mediati ng NE-induced chronotropy were altered by hypoxia.