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

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 5th 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.

The adaptive role of nitric oxide and hydrogen sulphide in vasoactive responses of thoracic aorta is triggered already in young spontaneously hypertensive rats.

The aorta plays an important role in blood pressure control so the early determination of its vasoactive properties could predict pathological changes in hypertension. The aim of study was to compare vasoactive properties and geometry of thoracic aorta (TA) and the participation of two vasoactive transmitters, nitric oxide (NO) and hydrogen sulphide (H2S), in TA tone regulation in young Wistar rats (WR) and spontaneously hypertensive rats (SHR). Four-weeks-old WR and SHR were used. Systolic blood pressure (sBP) was measured by plethysmography. The vasoactivity of TA was evaluated by changes in isometric tension. For morphological study the geometry of TA was measured using light microscopy. Decomposition of NO donor (nitrosoglutathione, GSNO) induced by H2S donor (Na2S) was studied by UV-VIS spectroscopy. In SHR the sBP was not increased in spite of cardiac hypertrophy compared to WR. Vasoconstriction to noradrenaline (NA) was decreased in SHR compared to WR which correlated with arterial wall hypotrophy. Acetylcholine (Ach)-induced vasorelaxation was increased and NO component participated in vasorelaxation and basal tone regulation significantly more in SHR. Na2S induced biphasic effect in both experimental groups, however, the shift towards vasorelaxation was demonstrated in SHR. Pretreatment with NO-synthase inhibitor, NG-nitro-L-arginine methylester (L-NAME), diminished the contractile part of vasoactive Na2S effects in both strains, moreover, an increased sensitivity in behalf of vasorelaxation was observed in SHR. Pretreatment with Na2S did not affect Ach-induced vasorelaxation in WR, but an inhibition was demonstrated in SHR. On the other hand, pretreatment with Na2S increased the release of NO from GSNO which corresponded with increased GSNO-induced vasorelaxation in both groups. However, this effect was stronger in SHR. The study showed that TA of prehypertensive SHR disposed by decreased contractility and strengthened endothelium-regulated vasorelaxant mechanisms involving of NO and H2S interaction which could serve as adaptive mechanisms in the adulthood.

Captopril partially decreases the effect of H(2)S on rat blood pressure and inhibits H(2)S-induced nitric oxide release from S-nitrosoglutathione.

We studied the effects of the H(2)S donor Na(2)S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na(2)S (1-4 micromol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 micromol/kg, Na(2)S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H(2)S influences MAP and heart and breathing rates. The effect of Na(2)S in decreasing MAP was less pronounced in the presence of captopril (2 micromol/l), which may indicate that the renin-angiotensin system is partially involved in the Na(2)S effect. Captopril decreased H(2)S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H(2)S. These results contribute to the understanding of the effects of H(2)S on the cardiovascular system.