ATP, alpha,beta-methylene ATP and suramin as tools for characterization of vascular P2x receptors in the pithed rat

Abstract

1. In pithed rats, the blood pressure effects of ATP, alpha,beta-methylene ATP (mATP), alpha-adrenoreceptor agonists and of electrical stimulation of the thoracolumbar sympathetic outflow were studied in the absence and presence of mATP, suramin and adrenoreceptor antagonists. 2. ATP elicited an initial rise in mean blood pressure followed by a decrease and a second increase. mATP produced a short-lived increase in blood pressure, whereas equieffective doses of noradrenaline, methoxamine and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(5,4-d)-azepine) produced a more prolonged, biphasic pressor response. 3. In the presence of high doses of prazosin, rauwolscine plus propranolol, the initial vasopressor and the vasodepressor effect to ATP were not affected, whereas the delayed vasopressor response to ATP, the vasopressor response to electrical stimulation and even more so that to noradrenaline were suppressed. 4. Suramin, which by itself produced a short-lived decrease, followed by a persistent increase in blood pressure, decreased the pressor responses to ATP (initial phase), to mATP and to electrical stimulation without affecting the fall and second rise in blood pressure elicited by ATP and the pressor response to noradrenaline. 5. Desensitization of P2x receptors by a low dose of mATP abolished the initial vasopressor response to ATP but failed to affect the subsequent blood pressure effects of ATP as well as the pressor responses to noradrenaline and electrical stimulation. A high dose of mATP, in addition, decreased the vasopressor responses to noradrenaline, methoxamine, B-HT 920 and electrical stimulation; the delayed effects of ATP on blood pressure were not changed. 6. The electrically induced increase in blood pressure subsequent to administration of high doses of prazosin, rauwolscine plus propranolol was diminished by suramin and by the low and high dose of mATP. 7. The present study suggests that under certain circumstances ATP, which, added exogenously, has a triphasic effect on mean blood pressure, contributes to the electrically induced vasopressor response by activation of P2x receptors.