Vasodilator responses to ATP and UTP are not dependent on nitric oxide release, K+(ATP) channel activation, or the release of vasodilator prostaglandins in the hindlimb vascular bed of the cat.
The effects of the purinergic agonists, ATP, ATPgammaS, UTP, and 2-Met-Thio AP, were investigated in the hindlimb vascular bed of the cat. Under constant-flow conditions, injections of the purinergic agonists into the perfusion circuit elicited dose-related decreases in perfusion pressure. The order of potency was 2-Met-Thio ATP > ATPgammaS > ATP > UTP. In contrast, injections of GTPgammaS, cAMP, UDP, and UMP had no effect. Vasodilator responses to ATP, ATPgammaS, UTP, and 2-Met-Thio ATP were increased in duration by the cAMP phosphodiesterase inhibitor rolipram, whereas the cGMP phosphodiesterase inhibitor zaprinast had no effect. Responses to the purinergic agonists were not altered by nitric oxide synthase inhibitors, K+(ATP) channel antagonists, cyclooxygenase inhibitors, or agents that interfere with the actions of the adrenergic nervous system. These data suggest that ATP, ATPgammaS, UTP, and 2-Met-Thio ATP dilate the hindlimb vascular bed by a direct cAMP-dependent mechanism, and that the release of nitric oxide, vasodilator prostaglandins, K+(ATP) channel opening, or an inhibitory effect on the adrenergic nervous system play little, if any, role in mediating or modulating responses to the purinergic agonists in the hindlimb circulation of the cat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010646:Phentolamine / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D011688:Purinones / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; D011453:Prostaglandins; D011688:Purinones; D009569:Nitric Oxide; D012110:Reserpine; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; C011145:zaprinast; D014544:Uridine Triphosphate; D010646:Phentolamine