Partially endothelium-dependent vasodilator effect of adenosine in rat aorta.
The vasodilator effect of adenosine on the contraction induced by phenylephrine, an alpha 1-adrenergic receptor agonist, was investigated in the isolated rat aorta. We found that the effect of adenosine was greater in intact aortas than in endothelium-denuded preparations. Denuding caused a parallel shift of the dose-response curve of adenosine to the right by a factor of five in comparison with intact aorta. This finding indicates that the relaxing effect of adenosine is partially endothelium-dependent in rat aorta. The mechanism of action of adenosine on vascular smooth muscle was also investigated in receptor-mediated and voltage-dependent calcium influx experiments performed with the addition of phenylephrine and high potassium concentrations, respectively. Although adenosine significantly inhibited only the tonic phase of the contraction induced by phenylephrine (10(-5) M), it did so to both the fast and slow phases of the contraction produced by high potassium concentrations (75 mM) with no preferential difference. In comparison to verapamil, a calcium entry blocker, adenosine behaved in a manner similar to that of verapamil in counteracting the constriction induced by either phenylephrine or potassium. We conclude that the vasodilator effect of adenosine is partially endothelium-dependent and that the mechanism of this effect may involve the inhibition of calcium influx and the release of an endothelium-derived relaxing factor.
Yen
M H
MH
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Wu
C C
CC
Chiou
W F
WF
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D007537:Isometric Contraction; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D001688:Biological Products; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D014700:Verapamil; D000241:Adenosine; D011188:Potassium; D002118:Calcium