Comparative responses to alpha,beta-methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds.
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 AT(1) 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.
Bivalacqua
Trinity J
TJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Champion
Hunter C
HC
Shah
Mrugeshkumar K
MK
De Witt
Bracken J
BJ
Inscho
Edward W
EW
Kadowitz
Philip J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010477:Perfusion; D011312:Pressure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058919:Purinergic P2 Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D011942:Receptors, Adrenergic, alpha; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; C002630:alpha,beta-methyleneadenosine 5'-triphosphate