Vasodilator Responses to ATP and UTP are cAMP Dependent in the Mesenteric Vascular Bed of the Cat

Background: This study was designed to examine the responses to and the mechanism by which purinergic agonists decrease vascular resistance in the mesenteric vascular bed of the cat. Methods and Results: Injections of ATP, UTP, and 2-MethylThioATP (2-MetSATP) into the mesenteric perfusion circuit elicited dose-dependent decreases in perfusion pressure while injections of P,y-MethylATP (f3,y-MetATP) produced a biphasic response with an initial vasopressor response followed by a vasodilator response. The order of potency of the vasodilator response was 2-MetSATP > ATP > UTP > P,y-MetATP. The vasodilator responses to ATP, UTP, 2-MetSATP, and P,y-MetATP were increased in duration by the cAMP phosphodiesterase inhibitor, rolipram. However, vasodilator responses were not altered by the adminstration of a nitric oxide synthase inhibitor, a cGMP phosphodiesterase inhibitor, or a cyclooxygenase inhibitor. Treatment with PPADS, a P2X,, P2Y, and P2Y4 receptor antagonist, did not alter vasodilator responses to the purinergic agonists; however, the vasopressor component of the response to P,y-MetATP was decreased. Conclusions: These data suggest that ATP, UTP, 2-MetSATP, and P,Y-MetATP dilate the mesentary vascular bed in the cat by a cAMP dependent mechanism, and that nitric oxide or prostaglandin release, cGMP accumulation, or activation of P2X,, P2Y, or P2Y4 receptors play little or no role in mediating vasodilator responses to the purinergic agonists in this regional vascular bed. In addition, these results suggest that the pressor component of the response to P,y-MetATP is mediated by the activation of P2X, receptors.