Basal tonic release of nitric oxide coupled to cGMP production regulates the vascular reactivity of the mesenteric bed

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.