Investigation of the selectivity of alpha, beta-methylene ATP in inhibiting vascular responses of the rat in vivo and in vitro.

1. The proposal that alpha,beta-methylene adenosine 5'-triphosphate (mATP) inhibits pressor responses in the pithed rat by selective desensitization of P2x-purinoceptors was examined by comparing the selectivity of its inhibitory effect on vascular responses in vitro and in vivo. 2. In isolated ring preparations of rat femoral and tail artery, which had been denuded of endothelium, mATP markedly reduced the contractile response to exogenous ATP but had no effect on the response of the arteries to exogenous noradrenaline (NA). 3. In the pithed rat a substantial proportion of the pressor response to sympathetic nerve stimulation was resistant to alpha-adrenoceptor blockade, suggesting a non-adrenergic component to the sympathetic vasoconstriction. 4. In the pithed rat, repeated administration of desensitizing doses of mATP attenuated the pressor response to sympathetic nerve stimulation by approximately 80%, suggesting that a component of the sympathetic vasoconstriction is mediated by ATP acting on vascular P2x-purinoceptors. However, the same mATP treatment also attenuated, to a similar degree, the pressor responses to intravenous NA, angiotensin II and vasopressin, indicating that the desensitization procedure was non-selective. 5. These results demonstrate that while mATP can be used to desensitize selectively P2x-purinoceptors in vitro, its attenuation of the sympathetic nerve-mediated pressor response in vivo is non-selective.