PMID- 11672566 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 424 IP - 3 DP - 2001 Jul 27 TI - Basal tonic release of nitric oxide coupled to cGMP production regulates the vascular reactivity of the mesenteric bed. PG - 221-7 AB - To reveal a basal production of nitric oxide (NO) and guanosine 3',5' cyclic 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 significantly reduced the release of NO and tissue cGMP. A significant correlation between these messengers was shown. Blockade of soluble guanylyl cyclase with 0.3-10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) only reduced basal cGMP production; 1-100 nM sildenafil (Sild), an inhibitor of phosphodiesterase V, increased basal tissue cGMP without modifying the release of NO. Acetylcholine (0.01-10 microM) caused a concentration-dependent rise in NO and cGMP evoking a proportional vasodilatation, demonstrating the interdependence between these messengers and vascular reactivity. Endothelium removal 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 significantly altering luminal NO release. The present results highlight a tonic release of NO and its involvement in endothelial-smooth muscle signaling; NO and cGMP are determinants of vascular reactivity. FAU - Buvinic, S AU - Buvinic S AD - Centro de Regulacion Celular y Patologia, Instituto Milenio de Biologia Fundamental y Aplicada, MIFAB, P. Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. FAU - Huidobro-Toro, J P AU - Huidobro-Toro JP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one) RN - 0 (Enzyme Inhibitors) RN - 0 (Oxadiazoles) RN - 0 (Piperazines) RN - 0 (Purines) RN - 0 (Quinoxalines) RN - 0 (Sulfones) RN - 0 (Vasoconstrictor Agents) RN - 0 (Vasodilator Agents) RN - 2149-70-4 (Nitroarginine) RN - 31C4KY9ESH (Nitric Oxide) RN - 94ZLA3W45F (Arginine) RN - BW9B0ZE037 (Sildenafil Citrate) RN - H2D2X058MU (Cyclic GMP) RN - N9YNS0M02X (Acetylcholine) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Acetylcholine/pharmacology MH - Animals MH - Arginine/pharmacology MH - Cyclic GMP/*biosynthesis MH - Dose-Response Relationship, Drug MH - Endothelium, Vascular/physiology MH - Enzyme Inhibitors/pharmacology MH - Male MH - Mesenteric Arteries/drug effects/metabolism/*physiology MH - Nitric Oxide/*metabolism MH - Nitroarginine/pharmacology MH - Norepinephrine/pharmacology MH - Oxadiazoles/pharmacology MH - Piperazines/pharmacology MH - Purines MH - Quinoxalines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Sildenafil Citrate MH - Sulfones MH - Vasoconstriction/drug effects MH - Vasoconstrictor Agents/pharmacology MH - Vasodilation/drug effects/*physiology MH - Vasodilator Agents/pharmacology EDAT- 2001/10/24 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/10/24 10:00 PHST- 2001/10/24 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/10/24 10:00 [entrez] AID - S0014299901011657 [pii] AID - 10.1016/s0014-2999(01)01165-7 [doi] PST - ppublish SO - Eur J Pharmacol. 2001 Jul 27;424(3):221-7. doi: 10.1016/s0014-2999(01)01165-7.