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.
Kawana
S
S
Department of Anesthesiology, School of Medicine, Sapporo Medical University, Japan.
Kimura
H
H
Miyamoto
A
A
Ohshika
H
H
Namiki
A
A
D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D015687:Cell Hypoxia; D002462:Cell Membrane; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000187:drug effects / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine