The effect of Cu2+ on rat pulmonary arterial rings

Abstract In the current study, Cu 2+ 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 Cu 2+ . N G - Monomethyl- l -arginine abolished both the copper-induced relaxation and the increase in cGMP of rings. Cu 2+ and zaprinast, which inhibits phosphodiesterase activity, caused a synergistic increase in cGMP level in the rings, suggesting that Cu 2+ 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 Cu 2+ and acetylcholine was additive, not synergistic. Cu 2+ did not augment relaxation induced by exogenously added NO donor. These results suggest that Cu 2+ 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.