Comparison between endothelial and neuronal nitric oxide pathways in rat aorta and gastric fundus.
This study examines the ability of different nitric oxide synthase (NOS) inhibitors and NO donors to inhibit the endothelium-dependent relaxation of the rat aorta and the NANC relaxation of the rat gastric fundus. NG-Nitro-L-arginine, N-monomethyl-L-arginine, and S-methyl-L-thiocitrulline elicite comparable potency in the aorta and in the fundus. However, 1-(2-trifluoromethyl)imidazole (TRIM), unlike 7-nitroindazole, is more potent on the fundus than on the aorta, showing that TRIM elicits a selective functional inhibition of the neural NOS isoform. (1H)-(1,2,4)Oxadiazole(4,3-a)quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase, inhibits the dilator response in both tissues and the cyclic GMP mimetic, 8-Br-cGMP, is 16 times more potent for inducing relaxation in the gastric fundus than in the aorta. However, methylene blue and LY-83583, two other inhibitors of soluble guanylyl cyclase and superoxide anion-generating agents, are at least 100 times less potent on fundus strips than on aortic rings. The data suggest that once released into the extracellular space, NO is more susceptible to inactivation by superoxide anions in the vascular tissue than in the gastric fundus. Thus, the study shows that selective inhibition of NO in a target tissue may be reached not only at the NOS isoform level but also by the manipulation of the NO pathway.
Guilmard
C
C
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Auguet
M
M
Chabrier
P E
PE
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP