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

Pierre-Antoine Crassous,Annie Beuve,Xavier Fioramonti,Zongmin Zhou,Padma Baskaran,Samba Couloubaly,Andreas Papapetropoulos,David D Kim,Walter N Durán

doi:10.1186/1471-2210-11-s1-o33

Pierre-Antoine Crassous, Annie Beuve + Show 7 more

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https://doi.org/10.1186/1471-2210-11-s1-o33

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Abstract

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.

Highlights

We recently discovered that soluble guanylyl cyclase activity is modulated by S-nitrosation, the addition of a NO moiety to the free thiol of cysteines (Cys)
As nitroglycerin-induced tolerance is a model of oxidative vascular dysfunction with increase in superoxide generation, we hypothesized that soluble guanylyl cyclase (sGC) activity could be affected in some types of oxidative cardiovascular diseases (CVD) via oxidation of its thiols
We found that Angiotensin II (Ang II) treatment (100nM, 4h) of A7r5 SMC infected with sGC-expressing adenoviruses reduces NOstimulated activity by 50% and induces strong S-nitrosation of sGC

Summary

Introduction

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). 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.

Results

Conclusion