S. Buvinic et Jp. Huidobro-toro, Basal tonic release of nitric oxide coupled to cGMP production regulates the vascular reactivity of the mesenteric bed, EUR J PHARM, 424(3), 2001, pp. 221-227
To reveal a basal production of nitric oxide (NO) and guanosine 3',5' cycli
c monophosphate (cGMP) in the rat arterial mesenteric bed, mesenteries were
perfused in the absence and in the presence of selective blockers of the L
-arginine cascade. Endothelium removal or inhibition of NO synthase signifi
cantly reduced the release of NO and tissue cGMP. A significant correlation
between these messengers was shown. Blockade of soluble guanylyl cyclase w
ith 0.3-10 muM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) only reduc
ed basal cGMP production; 1-100 nM sildenafil (Sild), an inhibitor of phosp
hodiesterase V, increased basal tissue cGMP without modifying the release o
f NO. Acetylcholine (0.01-10 muM) caused a concentration-dependent rise in
NO and cGMP evoking a proportional vasodilatation, demonstrating the interd
ependence between these messengers and vascular reactivity. Endothelium rem
oval or NO synthase blockade reduced the acetylcholine-induced increase of
messengers and the vasodilatation. ODQ attenuated only the increase in cGMP
and the vasodilatation, while sildenafil increased cGMP without significan
tly altering luminal NO release. The present results highlight a tonic rele
ase of NO and its involvement in endothelial-smooth muscle signaling; NO an
d cGMP are determinants of vascular reactivity. (C) 2001 Elsevier Science B
.V. All rights reserved.