Comparative responses to α,β-methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds

Abstract

Responses to the P2X-purinoceptor agonist α,β-methylene-ATP (α,β-MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of α,β-MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was α,β-MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > α,β-MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to α,β-MeATP was compared with responses to angiotensin II and U-46619. The P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid attenuated the pressor response to α,β-MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to α,β-MeATP were not altered by cyclooxygenase, α-adrenergic, or angiotensin AT1 antagonists. These data show that α,β-MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, α,β-MeATP had modest pressor activity in the systemic bed, where it was 1,000-fold less potent than angiotensin II. These data suggest that responses to α,β-MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed.