NO resistance in angiotensin II–induced hypertension is associated with S-nitrosation of soluble guanylyl cyclase

Background We recently discovered that soluble guanylyl cyclase (sGC) activity is modulated by S-nitrosation, the addition of a NO moiety to the free thiol of cysteines (Cys). Pathologically, we observed that exposure to low, therapeutic levels of nitroglycerin in rats led to decreased vascular response to NO in the arterioles of hamster cheek pouch, which correlated with S-nitrosation and desensitization of sGC. As nitroglycerin-induced tolerance is a model of oxidative vascular dysfunction with increase in superoxide generation, we hypothesized that sGC activity could be affected in some types of oxidative cardiovascular diseases (CVD) via oxidation of its thiols.