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J Appl Physiol 93: 1287-1295, 2002; doi:10.1152/japplphysiol.00262.2002
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Vol. 93, Issue 4, 1287-1295, October 2002

Comparative responses to alpha ,beta -methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds

Trinity J. Bivalacqua, Hunter C. Champion, Mrugeshkumar K. Shah, Bracken J. De Witt, Edward W. Inscho, and Philip J. Kadowitz

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Responses to the P2X-purinoceptor agonist alpha ,beta -methylene-ATP (alpha ,beta -MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of alpha ,beta -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 alpha ,beta -MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > alpha ,beta -MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to alpha ,beta -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 alpha ,beta -MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to alpha ,beta -MeATP were not altered by cyclooxygenase, alpha -adrenergic, or angiotensin AT1 antagonists. These data show that alpha ,beta -MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, alpha ,beta -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 alpha ,beta -MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed.

vasoconstrictor; pulmonary and peripheral vascular bed; pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid


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