Differential effects of hydroxocobalamin on relaxations induced by nitrosothiols in rat aorta and anococcygeus muscle.
In aortic rings, hydroxocobalamin (30 microM) reduced the relaxant actions of S-nitrosocysteine (0.1-3 microM), S-nitrosoglutathione (0.1-3 microM) and S-nitroso-N-acetylpenicillamine (SNAP, 0.01-3 microM), but did not affect the relaxant action of S-nitroso-coenzyme A (0.1-3 microM). In anococcygeus muscles, hydroxocobalamin (30 microM) had little effect on relaxations produced by nitrosocysteine (0.1-3 microM) and SNAP (0.01-1 microM), and enhanced those produced by nitrosoglutathione (0.1-3 microM) and nitroso-coenzyme A (0.1-3 microM). Since hydroxocobalamin is thought to act like haemoglobin by sequestering NO, some of the effects of hydroxocobalamin were compared with those of haemoglobin. Haemoglobin (10 microM) inhibited relaxations of aortic rings produced by nitrosocysteine and nitrosoglutathione and relaxations of anococcygeus muscles produced by nitrosocysteine, nitrosoglutathione and SNAP. Thus the effects of hydroxocobalamin on nitrosothiol-induced relaxations differ between the rat aorta and anococcygeus muscle, and depend on the exact nature of the nitrosothiol; however, the effects of haemoglobin did not differ qualitatively between the two tissues. Since hydroxocobalamin reduced relaxations of rat anococcygeus muscles elicited by NO, but not those elicited by nitrergic nerve stimulation or nitrosothiols, the nitrergic transmitter more closely resembles a nitrosothiol than free NO. Of those tested, the best correspondence was with nitrosocysteine; however, there were some differences between it and the transmitter.
Rand
M J
MJ
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Li
C G
CG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003065:Coenzyme A / Q000037:antagonists & inhibitors; D003545:Cysteine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D006454:Hemoglobins / Q000494:pharmacology; D006879:Hydroxocobalamin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009603:Nitroso Compounds / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
D006454:Hemoglobins; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; C084625:S-nitroso-coenzyme A; C021315:S-nitrosocysteine; D005978:Glutathione; D010396:Penicillamine; D003545:Cysteine; D006879:Hydroxocobalamin; D003065:Coenzyme A