Targeted and persistent effects of NO mediated by S-nitrosation of tissue thiols in arteries with endothelial dysfunction-

Authors
M. Sarr, M. Chataigneau, N. Etienne-Selloum, A. S. Diallo, C. Schott et al.

Lab
Pharmacologie & Physico-Chimie, UMR CNRS 7175 LC1, Illkirch, France ; Université Bordeaux 2, Laboratoire de Pharmacologie de l’UFR Pharmacie, Bordeaux, France.

Journal
Nitric Oxide

Abstract
We have previously demonstrated that in endothelium-denuded arteries, S-nitrosation of cysteine residues is a mechanism of formation of releasable nitric oxide (NO) stores, accounting for the long-lasting relaxation induced by S-nitrosating agents like S-nitrosoglutathione (GSNO). Here, we have investigated whether such effects could also be obtained in arteries exhibiting oxidative stress-associated endothelial dysfunction. Rats were implanted or not with a minipump delivering saline or angiotensin II for 14 days. As expected, aorta from angiotensin II-infused rats exhibited increased level of superoxide anions (as evaluated with dihydroethidine as fluorescent probe) and a reduced relaxation to acetylcholine in comparison to saline group. Unlike aortic rings with endothelium from controls, those from angiotensin II-infused rats exhibited persistent hyporesponsiveness to phenylephrine after pre-exposure to GSNO, as well as relaxation upon addition of N-acetylcysteine (NAC, which can displace NO from cysteine–NO residues) or HgCl2 (which cleaves S–NO bonds). In aorta from angiotensin II-infused rats, GSNO also induced a persistent increase in cysteine–NO residues (as determined using anti-cysteine–NO antiserum), which was blunted by NAC and HgCl2. These data indicate that (i) the vasorelaxant influence of releasable NO stores is unmasked by endothelial dysfunction (ii) S-nitrosation of cysteine residues remains an effective mechanism of formation of releasable NO stores in arteries exhibited oxidative stress-associated endothelial dysfunction. Thus, formation of releasable NO stores by S-nitrosating agents allows targeted vasculoprotective effects of NO at sites of endothelial dysfunction.

BIOSEB Instruments Used:
Non Invasive Pressure Measurement (LE5001),Cuffs and pulse transducers for LE 500X indirect blood pressure meters (LE5012)