Nitric oxide takes centre-stage with newly defined roles

McCall, Therese; Vallance, Patrick

doi:10.1016/0165-6147(92)90002-n

Cited by 145 publications

(58 citation statements)

References 8 publications

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“…However, as pointed out by Li & Rand (1989), the suggestion that there is some kind of store of transmitter (Thornbury et al, 1991) seems very unlikely given the rapid onset of action of the NOS inhibitors such as L-NOARG. Interestingly, our results do not rule out the possibility that CYSNO may be an important component of EDRF (Myers et al, 1990;McCall & Vallance, 1992), since hydroquinone does reduce relaxations to EDRF, although not those to the endogenous NANC transmitter (Hobbs et al, 1991).…”

Section: Discussionmentioning

confidence: 59%

“…These results provide strong evidence that NANC relaxations in this tissue, as in several others (Rand, 1992), involve the L-arginine: nitric oxide (NO) pathway, and that the neurotransmission system resembles that responsible for the production and release of the endothelium-derived relaxing factor (EDRF; Moncada et al, 1991). However, in both the endothelial (McCall & Vallance, 1992) and NANC (Gillespie & Sheng, 1989) systems there is still considerable debate over the nature of the substance actually released from the synthesizing cell, since several observations are difficult to reconcile with the release of free NO. Indeed, in the mouse anococcygeus we have demonstrated that hydroquinone, acting as a free radical scavenger, greatly reduces relaxations induced by NO, but has no effect on those to NANC nerve stimulation or several other nitrovasodilators (Hobbs et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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An investigation of some S‐nitrosothiols, and of hydroxy‐arginine, on the mouse anococcygeus

Gibson

Babbedge

Brave

et al. 1992

British J Pharmacology

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1 The effect of five S-nitrosothiols, and of the stereoisomers of N0-hydroxy-arginine (HOARG), were investigated on the mouse anococcygeus. 2 All five S-nitrosothiols produced concentration-related (0.1-100IM) relaxations of carbachol (50 LM)-induced tone; the order of potency was S-nitroso-L-cysteine (CYSNO)> S-nitroso-N-acetyl-D,Lpenicillamine (SNAP)>S-nitrosoglutathione (GSNO)> S-nitrosocoenzyme A (CoASNO)> S-nitroso-N-acetyl-L-cysteine (NACNO). The relaxations were unaffected by the nitric oxide synthase (NOS) inhibitor, L-NG-nitro-arginine (10 JIM) (L-NOARG).3 Cold-storage of the tissue for 72 h resulted in loss of sympathetic and non-adrenergic, noncholinergic (NANC) nerve function. NOS activity in the tissue was reduced by 97%. Despite this, relaxations induced by the S-nitrosothiols were unaffected. 4 Haemoglobin (50 jM) attenuated relaxations induced by NO and the S-nitrosothiols, although responses to 3-isobutyl-1-methyl-xanthine were unaffected. N-methyl-hydroxylamine (2 mM) which has been shown previously to produce selective inhibition of NANC and nitrovasodilator responses in this tissue, also reduced responses to all S-nitrosothiols.5 Hydroquinone (100 gM) greatly reduced relaxations to CYSNO (by 88%) but had no effect on those to SNAP, GSNO, CoASNO or NACNO. Since hydroquinone does not reduce responses to NANC stimulation, CYSNO is unlikely to be the NANC transmitter. 6 L-HOARG by itself (up to 100 piM) had no significant effect on carbachol-induced tone or on NANC (10 Hz; 10 s train every 100 s) relaxations. However, it produced reversal of the inhibitory effects of L-NOARG (10;pM), being only slightly less potent than L-arginine. D-HOARG was without effect. L-HOARG had no effect on relaxations induced by 1.51iM NO. 7 The results show that S-nitrosothiols are potent relaxants of the mouse anococcygeus; they act directly on the smooth muscle with a mechanism similar to NO and other nitrovasodilators. In addition, the results are consistent with L-HOARG being an intermediate in the biosynthesis of NO from L-arginine, although there is no evidence for it acting to stabilize NO extracellularly.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

An investigation of some S‐nitrosothiols, and of hydroxy‐arginine, on the mouse anococcygeus

Gibson

Babbedge

Brave

et al. 1992

British J Pharmacology

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“…In general, there are two types of NO synthase, one is the constitutive NO synthase and the other is the inducible one (2). The functional consequences of the formation of NO by the inducible NO synthase have not been clearly es tablished, but it is likely that it plays a role in pathological vasodilation and tissue damage (2,10). Arginine ana logues such as L-NAME are specific inhibitors of both the constitutive and inducible NO synthase (19).…”

Section: Discussionmentioning

confidence: 99%

“…Kitagawa et al (9) reported that L-arginine given intravenously prevented gastric lesions caused by 0.6 N HC1 or water-immersion stress, yet the mechanism remained unclarified. Since the intracellular levels of L-arginine are already high and the supply of L-ar ginine is not normally rate-limiting for the constitutive en zyme (2,10), it is ambiguous whether the protective ac tion of L-arginine is really mediated by the NO-dependent pathway.…”

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confidence: 99%

Cytoprotective Action of L-Arginine against HCl-Induced Gastric Injury in Rats: Involvement of Nitric Oxide?

Takeuchi

Ohuchi

Kato

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We examined the cytoprotective effect of L-arginine on gastric damage induced by 0.6 N HC1 in rats and investigated whether the mechanism of this action is related to the nitric oxide (NO)-mediated protection. The animals were given 0.6 N HCI by gavage and killed 1 hr later. L-Arginine (100, 300 and 750 mg/kg) given p.o. 30 min before HC1 treatment prevented these lesions in a dose-dependent manner, but had no effect when given i.v. (200 mg/kg). Similar effects were observed by D-arginine but not by an equimolar dose of mannitol. This effect of L-arginine (p.o.) was attenuated significantly by prior administra tion of indomethacin (5 mg/kg, s.c.) but not by NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg, i.v.), the NO synthase inhibitor. Both L and D-arginine produced a reduction in potential difference (PD), inhibi tion of gastric motility, and increases of luminal pH and mucosal blood flow when they were given intra gastrically. Indomethacin significantly mitigated these changes induced by L-arginine except PD reduction, while L-NAME showed significant inhibition only against the increased pH response. We conclude that L arginine given p.o. exhibits gastric cytoprotection against HCl-induced damage in rats, probably by acting as a mild irritant. The mechanism of this action may appear through "adaptive cytoprotection" mediated by endogenous prostaglandins and does not involve the NO-mediated protective pathway.

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“…Of interest to rheumatologists is growing evidence implicating NO in immune regulation, inflammation, autoimmunity, and arthritis. Named "molecule of the year" by Science in 1992 (14), this upwardly mobile mediator has been the subject of a spate of recent reviews (3)(4)(5)(15)(16)(17)(18)(19).…”

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confidence: 99%