Free-radical scavengers, thiol-containing reagents and endothelium-dependent relaxation in isolated rat and human resistance arteries.
1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force. 2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-omega-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone. 3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels. 4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-omega-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency. 5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation. 6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.
Sunman
W
W
Department of Clinical Pharmacology, St Mary's Hospital, Imperial College of Science Technology and Medicine, London, U.K.
Hughes
A D
AD
Sever
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PS
D000109:Acetylcholine / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries; D002216:Captopril / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D001120:Arginine; D002216:Captopril; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine; D009638:Norepinephrine