Endothelium-dependent contraction and -independent relaxation induced by adenine nucleotides and nucleoside in the canine basilar artery.
ATP, ADP, AMP and adenosine at 10(-8) induced a slight relaxation, and at concentrations greater than 10(-7) M caused a biphasic response consisting of an initial relaxation followed, after a brief period, by a transient contraction in canine basilar artery. ATP (10(-6) and 10(-5) M) caused a triphasic response consisting of a rapid, small contraction, a relaxation and then a second, transient contraction. The order of agonist potency for contraction was ATP greater than ADP much greater than AMP = adenosine, but for producing relaxation the agonists were equipotent. Removal of the endothelium abolished the contraction after the relaxation, but had virtually no effect on the relaxation and the rapid contraction induced by ATP (10(-6) and 10(-5) M). Only the relaxation in response to ATP (10(-6) M) was attenuated by removal of the endothelium. Aspirin (a cyclooxygenase inhibitor) (5 X 10(-5) M), OKY-046 (a thromboxane A2 synthetase inhibitor) (10(-5) M) and ONO-3708 (a thromboxane A2 antagonist) (5 X 10(-9) M) attenuated markedly the endothelium-dependent contraction induced by ATP (10(-5) M) and ADP (10(-5) M), but did not affect the relaxation. Phentolamine (10(-6) M) and atropine (10(-6) M) did not affect either the contraction or the relaxation. The relaxations induced by both ATP and adenosine in both endothelium-intact preparations and endothelium-removed preparations were attenuated by 8-phenyltheophylline (P1 antagonist) (10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Shirahase
H
H
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Usui
H
H
Manabe
K
K
Kurahashi
K
K
Fujiwara
M
M
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013928:Thromboxane A2 / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000227:Adenine Nucleotides; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate