The mechanism by which the purinergic agonist adenosine 5'-O-(3 thiotriphos
phate) (ATP gammaS) decreases vascular resistance was investigated in the m
esenteric and hindlimb vascular beds of the cat. Injections of ATP gammaS i
nto the hindlimb perfusion circuit elicited dose-dependent decreases in per
fusion pressure while injections into the mesenteric circuit produced a bip
hasic response with an initial vasopressor response followed by a vasodepre
ssor response. In the mesenteric vascular bed the pressor response to ATP g
ammaS was blocked by a P2X(1) receptor antagonist. Also an inhibitor of nit
ric oxide synthase enhanced the vasoconstrictive responses to ATP gammaS. H
owever, the vasodepressor response in the mesenteric bed was not altered by
the adminstration of an alpha adrenergic receptor antagonist, a cyclooxyge
nase inhibitor, a P2Y(1) receptor antagonist, or a K-ATP(+) channel blockin
g agent. These data suggest that the vasopressor response to ATP gammaS in
the mesenteric vascular bed of the cat is mediated via P2X(1) receptor acti
vation. The differential responses to ATP gammaS in the hindlimb and mesent
ery suggest differences in purinergic receptor distribution in the vascular
system of the cat. In addition, the results suggest that prostaglandin syn
thesis, P2Y(1) receptor activation, alpha receptor inhibition, and K-ATP(+)
channels activation play little to no role in mediating the vascular respo
nse to ATP gammaS in the mesentery of the cat. (C) 2001 Elsevier Science In
c. All rights reserved.