Smooth muscle relaxing effects of NO, nitrosothiols and a nerve-induced relaxing factor released in guinea-pig colon.
1. The aim of the present study was to compare the biological activity of S-nitroso-L-cysteine (CYSNO), S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and hydroxylamine to that of nitric oxide (NO) and a vascular relaxing factor released by nerve stimulation in the guinea-pig intestine. The biological activity was examined in a bioassay system with guinea-pig colon as donor tissue and a series of spiral strips of rabbit aorta without endothelium as detector tissues. 2. Electrical stimulation of the guinea-pig colon released a vascular relaxing factor. The half-life of the relaxing factor down the bioassay cascade was the same as exogenously applied NO. N omega-nitro-L-arginine (L-NOARG) inhibited the release of bioactivity. 3. The relaxations of the assay tissues caused by exogenous CYSNO also declined during the passage down the cascade. However, in the presence of L-cysteine (10(-5) M) the half-life of CYSNO increased and there was no significant breakdown through the cascade. In contrast, the half-life of applied NO and the vascular relaxing factor released by nerve stimulation was unaffected by the presence of L-cysteine. 4. Exogenously applied GSNO (20-50 nM), SNAP (2-4 nM) and hydroxylamine (300-600 nM) caused relaxations that did not decline during the passage down the cascade. 5. In summary, the relaxation of the bioassay tissues during nerve stimulation was indistinguishable from the relaxation induced by NO, whereas relaxations induced by CYSNO, GSNO, SNAP and hydroxylamine showed different pharmacological profiles. The released bioactivity is thus likely to be NO itself.
Iversen
H H
HH
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Gustafsson
L E
LE
Leone
A M
AM
Wiklund
N P
NP
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D014665:Vasodilator Agents / Q000494:pharmacology
D006898:Hydroxylamines; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D019811:Hydroxylamine; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D026423:S-Nitroso-N-Acetylpenicillamine; C021315:S-nitrosocysteine; D007501:Iron; D005996:Nitroglycerin; D010396:Penicillamine; D003545:Cysteine