Sympathetic nerve stimulation activates both beta 1- and beta 2-adrenoceptors of SA and AV nodes in anesthetized dog hearts.
We investigated blocking effects of the selective beta 1-adrenoceptor blocker atenolol (0.1-100 micrograms/kg, i.v.), the selective beta 2-adrenoceptor blocker ICI 118,551 (1-1000 micrograms/kg, i.v.) and the combination of the two drugs on positive chronotropic and dromotropic responses to norepinephrine (NE) released by stimulation of the sympathetic nerves in anesthetized, neurally decentralized, open-chest dogs after atropine was given. Stimulation of the intracardiac sympathetic nerves to the SA nodal region or to the AV nodal region selectively increased heart rate or decreased AV conduction time, respectively. ICI 118,551 inhibited the chronotropic or dromotropic response to each stimulation in a dose-dependent manner, but its inhibition of the dromotropic response was less than that of the chronotropic response. Atenolol similarly inhibited either the positive chronotropic or dromotropic response to each stimulation in a dose-related manner. The combination of atenolol and ICI 118,551 attenuated the responses to each stimulation more than atenolol alone. These data indicate that sympathetic nerve stimulation activates both beta 1- and beta 2-adrenoceptors of the SA and AV nodes and that the proportion of beta 2-adrenoceptor-mediated effects on the AV node is less than that on the SA node. These results suggest that neurally released NE in part controls physiological functional cardiac responses mediated through beta 2-adrenoceptors, in addition to the responses predominantly mediated through beta 1-adrenoceptors.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
M
M
Takei
Y
Y
Furukawa
M
M
Narita
M
M
Murakami
L M
LM
Ren
Y
Y
Karasawa
S
S
Chiba
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D001262:Atenolol; D009638:Norepinephrine