The inhibition of nitric oxide-mediated relaxations in rat aorta and anococcygeus muscle by diphenylene iodonium.
1. The effects of diphenylene iodonium (DPI), an inhibitor of reduced nicotinamide adenine dinucleotide phosphate-dependent oxidases (which generate superoxide anions), were studied on nitric oxide (NO)-mediated responses in isolated preparations of the rat aorta and anococcygeus muscle. 2. In aortic rings, the endothelium-dependent relaxant action of acetylcholine was reduced by DPI (0.3-10 mumol/L) in a concentration-dependent manner and abolished by the NO synthase (NOS) inhibitor L-nitro-NG-arginine methylester (L-NAME; 100 mumol/L). Relaxations induced by sodium nitroprusside (SNP) or NO were not affected by DPI or L-NAME. 3. In anococcygeus muscles, DPI (0.3-10 mumol/L) as well as L-NAME (5-100 mumol/L) produced concentration-dependent reductions of relaxations produced by nitrergic nerve stimulation. Relaxations induced by NO and SNP were not affected by either DPI or L-NAME. L-Arginine (1 mmol/L) prevented the reduction of nitrergic relaxations by L-NAME but not by DPI. 4. Contractions of anococcygeus muscles elicited by exogenous noradrenaline (1 mumol/L) were not affected or were inhibited by DPI (0.3-10 mumol/L), but the contractions elicited by noradrenergic nerve stimulation were significantly enhanced by DPI and L-NAME. When noradrenergic contractions had already been maximally enhanced by L-NAME (100 mumol/L), DPI produced no further enhancement. L-Arginine (1 mmol/L) prevented the enhancement of noradrenergic contractions by L-NAME but not by DPI. 5. The efflux of radioactivity induced by field stimulation from anococcygeus muscles previously incubated with [3H]-noradrenaline was not affected by either DPI or L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
Rand
M J
MJ
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Li
C G
CG
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D009861:Onium Compounds / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology
D009861:Onium Compounds; D010656:Phenylephrine; D009569:Nitric Oxide; C007517:diphenyleneiodonium; D001120:Arginine; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine