Manganese potentiation of nitric oxide-mediated vascular relaxation.
The half-life of nitric oxide (NO) and the relaxation of aortic-rings are enhanced by superoxide dismutase. Manganese and manganese-containing preparations have been reported to mimic superoxide dismutase activity. In the current study, manganese was tested for its ability to potentiate the activity of NO both in vitro and in vivo. Manganese relaxation of aortic segments was endothelium dependent as well as concentration dependent. Cyclic GMP concentrations in the segments were increased 2- and 4-fold with 5 and 300 microM manganese, respectively. N-Monomethyl-L-arginine pretreatment of aortic rings abolished the relaxation and cyclic GMP accumulation mediated by manganese. Infusion of manganese into conscious, restrained rats resulted in a decrease of blood pressure which was abolished by N-nitro-L-arginine pretreatment. Therefore, manganese may prolong the half-life of NO by a mechanism that mimics the action of superoxide dismutase resulting in potentiation of NO actions in vascular tissue.
Kasten
T P
TP
Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, MO.
Settle
S L
SL
Misko
T P
TP
Currie
M G
MG
Nickols
G A
GA
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D008345:Manganese; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP