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

• Published in: British journal of pharmacology Vol. 107; no. 3; pp. 715 - 721
• Main Authors: Gibson, A., Babbedge, R., Brave, S.R., Hart, S.L., Hobbs, A.J., Tucker, J.F., Wallace, P., Moore, P.K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.1992; Nature Publishing
• Subjects: Animals; Antimetabolites - pharmacology; Arginine - analogs & derivatives; Arginine - pharmacology; Autonomic Nervous System - drug effects; Biological and medical sciences; Carbachol - pharmacology; Cold Temperature; Cold‐storage; Fundamental and applied biological sciences. Psychology; haemoglobin; Hemoglobins - physiology; hydroquinone; Hydroquinones - pharmacology; hydroxy‐arginine; In Vitro Techniques; Male; Mercaptoethanol; Mice; mouse anococcygeus; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscles - drug effects; nitric oxide synthase; Nitroso Compounds - pharmacology; nitrosothiol; non‐adrenergic; non‐cholinergic; S-Nitrosothiols; Stereoisomerism; Striated muscle. Tendons; Vertebrates: osteoarticular system, musculoskeletal system; Nitroso compound; Stereoisomer; Thiol; Rodentia; Cold storage; In vitro; Hydroquinone; Vertebrata; Mammalia; Mouse; NANC transmission; Animal; Nitrogen monoxide; Hemoglobin
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb14512.x

1 The effect of five S‐nitrosothiols, and of the stereoisomers of NG‐hydroxy‐arginine (HOARG), were investigated on the mouse anococcygeus. 2 All five S‐nitrosothiols produced concentration‐related (0.1–100 μm) relaxations of carbachol (50 μm)‐induced tone; the order of potency was S‐nitroso‐l‐cysteine (CYSNO) > S‐nitroso‐N‐acetyl‐d,l‐penicillamine (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 μm) (l‐NOARG). 3 Cold‐storage of the tissue for 72 h resulted in loss of sympathetic and non‐adrenergic, non‐cholinergic (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 μm) 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 μm) 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 μm) 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 μm), being only slightly less potent than l‐arginine. d‐HOARG was without effect. l‐HOARG had no effect on relaxations induced by 1.5 μm 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.