The effect of Cu2+ on rat pulmonary arterial rings.
In the current study, Cu2+ was tested for its ability to relax vessels and to accumulate cyclic GMP (cGMP) in rat pulmonary artery employing rat extrapulmonary arterial rings. Cu(2+)-induced relaxation was endothelium and concentration (in the range from 10(-7) to 10(-4) M) dependent. The content of cGMP in the rings was increased 1.7-fold with 10(-4) M Cu2+. NG-Monomethyl-L-arginine abolished both the copper-induced relaxation and the increase in cGMP of rings. Cu2+ and zaprinast, which inhibits phosphodiesterase activity, caused a synergistic increase in cGMP level in the rings, suggesting that Cu2+ enhanced cGMP level through a mechanism different from that of zaprinast, probably as a consequence of elevated accumulation of nitric oxide (NO). The magnitude of vasorelaxation observed due to simultaneous addition of Cu2+ and acetylcholine was additive, not synergistic. Cu2+ did not augment relaxation induced by exogenously added NO donor. These results suggest that Cu2+ elevates NO level in the rings not by prolonging the half-life of NO, but by activation of endothelial nitric oxide synthase and subsequently potentiating the action of NO on vascular tone.
Ohnishi
T
T
Third Department of Internal Medicine, Fukui Medical School, Japan.
Ishizaki
T
T
Sasaki
F
F
Ameshima
S
S
Nakai
T
T
Miyabo
S
S
Matsukawa
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003300:Copper / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D010656:Phenylephrine; D009569:Nitric Oxide; D003300:Copper; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D000109:Acetylcholine