Vascular effects to ATPγS are bed dependent in the cat

The vascular receptor that which ATPγS, a stable nucleotide analog of ATP, interacts with is not fully understood. ATPγS has been shown to interact with P2x, P2y, and P2u receptors mediating vasoconstriction in some vascular beds and vasodilatation in others. The vascular responses to ATPγS were investigated in the mesenteric and hindlimb vascular bed of the cat. Under conditions of constant blood flow, ATPγS induced a dose dependent biphasic response characterized by an initial pressor response followed by a secondary dilatory response in the mesenteric vascular bed of the cat. However in the hindlimb of the cat, ATPγS produced a dose dependent vasodilator response with no constrictor phase. The vasoconstrictor responses to ATPγS in the mesentery were attenuated after the administration of PPADS, a P2x selective antagonist, but not by the angiotensin II AT1 receptor antagonist, candesarten, the alpha-adrenergic blocking agent, phentolamine, the cyclooxygenase inhibitor, meclofenamate, or by the K⁺_ATP channel antagonist, U-37883A. Moreover, the vasodilator component of the response to ATPγS was not attenuated by meclofenamate or L-NAME in either the mesenteric or hindlimb vascular beds. These data suggest that the vascular responses to ATPγS vary with vascular bed studied in that biphasic responses were observed in the mesenteric vascular bed while only vasodilator responses were observed in the hindlimb vascular bed. Since the constrictor component of the response is reduced by PPADS, these data may be interpreted to suggest that response in the mesentery are mediated by the activation of P2x receptors which are unevenly distributed in the vasculature of the cat. The results of the present study demonstrate that responses to ATPγS are not mediated by the adrenergic nervous system, activation of AT1 receptors, K⁺_ATP channels, or the release of NO, PGI₂, or TXA₂.