Nitroso-sulfide coupled signaling triggers specific vasoactive effects in the intrarenal arteries of patients with arterial hypertension

Abstract

In normotensive conditions, it has been confirmed that S-nitrosothiols (RSNO), can interact with hydrogen sulfide (H₂S) and create new substances with specific vasoactive effects. This interaction could also represent a new regulator signaling pathway in conditions of hypertension. Until now, these effects were studied only in normotensive rats, and they have not been carried out in humans yet. We investigated the vasoactive effects of the products of the H₂S/S-nitrosoglutathione (S/GSNO) interaction in lobar arteries (LA) isolated from the nephrectomized kidneys of patients suffering from arterial hypertension and in renal arteries (RA) of spontaneously hypertensive rats (SHR). The changes in the isometric tension of pre-contracted arteries were evaluated. Acetylcholine-induced vasorelaxation of LA was reduced compared to the effect induced by an NO donor, sodium nitroprusside suggesting an endothelium dysfunction. While 1 μmol/L Na2S had a minimal effect on the vascular tone, the concentration 20 μmol/L evoked a slight vasorelaxation. GSNO at 0.1 μmol/L induced vasorelaxation, which was less pronounced compared to the effect induced by 1 μmol/L. The S/GSNO products (final concentration 0.1 μmol/L) prepared as the mixture of GSNO (0.1 μmol/L) + Na2S (1 μmol/L) induced a higher vasorelaxation compared to GSNO (0.1 μmol/L) alone only in the 5^th minute and without the differences in the speed. On the other hand, the S/GSNO products (final concentration 1 μmol/L) prepared as the mixture of GSNO (1 μmol/L) + Na2S (10 μmol/L) induced a higher and faster vasorelaxation compared to the effect induced by GSNO (1 μmol/L) alone. In RA of SHR this S/GSNO products induced similar vasorelaxation (higher and faster than GSNO) with involvement of HNO (partially) and cGMP as mediators. However, the products of the H₂S/NO donor (DEA NONOate) manifested differently than S/GSNO indicating the unique interaction between GSNO and H₂S. In this study, we confirmed for the first time that specific vasoactive effects of coupled nitroso-sulfide signaling were also triggered in human arterial tissue. We suggest that in hypertension, H₂S in interaction with GSNO regulated a vasoconstrictor-induced increase in arterial tone towards a stronger vasorelaxation compared to GSNO alone or H₂S alone.