Alpha 2-adrenoceptor stimulation can augment coronary vasodilation maximally induced by adenosine in dogs.
To determine whether alpha 2-adrenoceptor stimulation can augment adenosine-induced coronary vasodilation, 34 open-chest dogs were studied. When a small dose of clonidine (up to 0.24 micrograms.kg-1.min-1 ic) was administered under beta-adrenoceptor blockade, coronary blood flow [312 +/- 16 (SE) ml.100 g-1.min-1] maximally induced by intracoronary infusion of adenosine was further increased (P less than 0.05) by 66 +/- 16 ml.100 g-1.min-1, despite no significant changes in coronary perfusion pressure, myocardial oxygen consumption, and coronary venous adenosine concentration. However, when a larger dose of clonidine (0.36-0.60 micrograms.kg-1.min-1) was infused, adenosine-induced flow progressively decreased. This biphasic action of the alpha 2-adrenoceptor activity was also observed when the dose of norepinephrine was increased during alpha 1-adrenoceptor blockade with prazosin. Norepinephrine up to 0.24 micrograms.kg-1.min-1 (ic) further increased adenosine-induced coronary blood flow by 24 +/- 5% (P less than 0.001), whereas hyperemic flow was decreased by a larger dose of norepinephrine. In contrast to the alpha 2-adrenoceptor stimulation, the alpha 1-adrenoceptor stimulation (norepinephrine with yohimbine) progressively decreased coronary blood flow. Furthermore, with a small dose of clonidine, reactive hyperemic flow significantly increased compared with that without clonidine (303 +/- 13 vs. 355 +/- 13 ml.100 g-1.min-1, P less than 0.001), but a larger dose of clonidine adversely reduced reactive flow (254 +/- 18 ml.100 g-1.min-1, P less than 0.001). Adenosine release during reactive hyperemia with and without intracoronary infusions of clonidine were not altered significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Hori
M
M
First Department of Medicine, Osaka University School of Medicine, Japan.
Kitakaze
M
M
Tamai
J
J
Iwakura
K
K
Kitabatake
A
A
Inoue
M
M
Kamada
T
T
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003000:Clonidine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D011983:Receptors, Purinergic; D011433:Propranolol; D000241:Adenosine; D003000:Clonidine