Vasodilator responses to ATP and UTP are cAMP dependent in the mesenteric vascular bed of the cat.
BACKGROUND
This study was designed to examine the responses to and the mechanism by which purinergic agonists decrease vascular resistance in the mesenteric vascular bed of the cat.


RESULTS
Injections of ATP, UTP, and 2-MethylThioATP (2-MetSATP) into the mesenteric perfusion circuit elicited dose-dependent decreases in perfusion pressure while injections of beta,gamma-MethylATP (beta,gamma-MetATP) produced a biphasic response with an initial vasopressor response followed by a vasodilator response. The order of potency of the vasodilator response was 2-MetSATP > ATP > UTP > beta,gamma-MetATP. The vasodilator responses to ATP, UTP, 2-MetSATP, and beta,gamma-MetATP were increased in duration by the cAMP phosphodiesterase inhibitor, rolipram. However, vasodilator responses were not altered by the adminstration of a nitric oxide synthase inhibitor, a cGMP phosphodiesterase inhibitor, or a cyclooxygenase inhibitor. Treatment with PPADS, a P2X(1), P2Y(1), and P2Y(4) receptor antagonist, did not alter vasodilator responses to the purinergic agonists; however, the vasopressor component of the response to beta,gamma-MetATP was decreased.


CONCLUSIONS
These data suggest that ATP, UTP, 2-MetSATP, and beta,gamma-MetATP dilate the mesentary vascular bed in the cat by a cAMP dependent mechanism, and that nitric oxide or prostaglandin release, cGMP accumulation, or activation of P2X(1), P2Y(1), or P2Y(4) receptors play little or no role in mediating vasodilator responses to the purinergic agonists in this regional vascular bed. In addition, these results suggest that the pressor component of the response to beta,gamma-MetATP is mediated by the activation of P2X(1) receptors.
Shah
M K
MK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
Bivalacqua
T J
TJ
Champion
H C
HC
Kadowitz
P J
PJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011688:Purinones / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D011688:Purinones; D013873:Thionucleotides; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; C011145:zaprinast; D020889:Rolipram; D014544:Uridine Triphosphate; D019331:NG-Nitroarginine Methyl Ester; C008501:2-methylthio-ATP