AUTHOR=Perrin-Sarrado Caroline , Pongas Marios , Dahboul Fatima , Leroy Pierre , Pompella Alfonso , Lartaud Isabelle 

TITLE=Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings

JOURNAL=Frontiers in Physiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2016.00630

DOI=10.3389/fphys.2016.00630

ISSN=1664-042X

ABSTRACT=<p><bold>Aims:</bold> Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from <italic>S</italic>-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO.</p><p><bold>Methods:</bold> Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20–22 weeks—submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: E<sub>max</sub>; pD<sub>2</sub>) to carbachol or sodium nitroprusside to evaluate endothelial dependent or independent NO-induced vasodilation, or GSNO (exogenous NO vasodilation depending from the endothelial GGT activity). GGT activity was measured using a chromogenic substrate in aortic homogenates. Its role in GSNO-induced relaxation was assessed following inhibition of the enzyme activity (serine-borate complex). That of protein disulfide isomerase (PDI), another redox sensitive enzyme involved in GSNO metabolism, was assessed following inhibition with bacitracin.</p><p><bold>Results:</bold> Aortic GGT activity (18–23 μmol/min/mg of tissue in adult WKY) decreased by 33% in SHR and 45% in SHR with high salt diet. E<sub>max</sub> and pD<sub>2</sub> for sodium nitroprusside were similar in all groups. E<sub>max</sub> for carbachol decreased by −14%, reflecting slight endothelial NO-dependent dysfunction. The GSNO curve was slightly shifted to the left in SHR and in SHR with high salt diet, showing a small enhanced sensitivity to GSNO. Involvements of GGT, as that of PDI, in the GSNO effects were similar in all groups (pD<sub>2</sub> for GSNO −0.5 to −1.5 following enzymatic inhibition).</p><p><bold>Conclusion:</bold> Hypertension is associated with a decreased aortic GGT activity without decreasing the vasorelaxant effects of GSNO, whose bioactivity may be supplemented through the alternative enzymatic activity of PDI.</p>