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, ATP gamma S, UTP, and 2-Met-Th io AP, were investigated in the hindlimb vascular bed of the cat. Under con stant-flow conditions, injections of the purinergic agonists into the perfu sion circuit elicited dose-related decreases in perfusion pressure. The ord er of potency was 2-Met-Thio ATP > ATPgammaS > ATP > UTP. In contrast, inje ctions of GTPgammaS, cAMP, UDP, and UMP had no effect. Vasodilator response s to ATP, ATPgammaS, UTP, and 2-Met-Thio ATP were increased in duration by the cAMP phosphodiesterase inhibitor rolipram, whereas the cGMP phosphodies terase inhibitor zaprinast had no effect. Responses to the purinergic agoni sts were not altered by nitric oxide synthase inhibitors, K-ATP(+) channel antagonists, cyclooxygenase inhibitors, or agents that interfere with the a ctions of the adrenergic nervous system. These data suggest that ATP, ATPga mmaS, 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 a drenergic nervous system play little, if any, role in mediating or modulati ng responses to the purinergic agonists in the hindlimb circulation of the cat.