Prolonged exposure of canine coronary arteries to a nitric oxide donor desensitizes soluble guanylate cyclase

Prolonged exposure of coronary arteries to SNP did not alter vascular smooth muscle function, but it markedly attenuated the relaxation in response to both A23187 and authentic NO at concentrations above 10−9 M in a concentration-dependent fashion. The constant levels of cGMP in response to an NO donor suggest that the attenuation of relaxation is due to desensitization of soluble guanylate cyclase. Thus, this study supports the role of soluble guanylate cyclase desensitization in the development of tolerance to organic nitrates.