Relaxing effects of adenosine in coronary artery in calcium-free medium.
Adenosine relaxes the coronary arteries of various species through A2 receptors. The mechanism(s) by which adenosine causes relaxation of the coronary smooth muscle through changes in intracellular Ca levels is not understood. Therefore, the aim of this study was to evaluate the vasodilatory action of adenosine in normal and in Ca-free medium and the effect of adenosine on 45Ca efflux in Ca-free medium. Prostaglandin F2 alpha (10(-5) M) was used to induce tone in bovine coronary artery rings both in the presence and absence of Ca. Adenosine, 5'-N-ethyl-carboxamide adenosine (NECA) and N6-L-phenyl-isopropyl adenosine (L-PIA) produced concentration-dependent relaxation of the coronary artery rings when precontracted with prostaglandin F2 alpha. Both in normal and Ca-free medium, the order of potency for adenosine analogs (NECA greater than L-PIA greater than adenosine) was similar and 8-phenyltheophylline antagonized the relaxation response to adenosine and its analogs. In Ca-free medium, the concentration-response curves for adenosine and its analogs were shifted to the right, in a parallel fashion, from the curves obtained in Ca-containing solution. Removal of extracellular Ca reduced the maximum responses and slowed the rate of relaxation of adenosine and its analogs and the KB values for 8-phenyltheophylline were significantly increased. In Ca-free medium, adenosine was without an effect on 45Ca efflux in the presence of prostaglandin F2 alpha. The data suggest that the coronary vasodilatory action of adenosine has both extracellular Ca-dependent and -independent components.
Ramagopal
M V
MV
Department of Pharmacology, School of Medicine, East Carolina University, Greenville 27858-4354.
Nakazawa
M
M
Mustafa
S J
SJ
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002132:Calcium Radioisotopes; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*
D002132:Calcium Radioisotopes; D015237:Dinoprost; D000241:Adenosine; D001920:Bradykinin; D002118:Calcium