Arterial Hypertension and Plasma Glucose Modulate the Vasoactive Effects of Nitroso-Sulfide Coupled Signaling in Human Intrarenal Arteries

Abstract

We have investigated the vasoactive effects of the coupled nitro-sulfide signaling pathway in lobar arteries (LAs) isolated from the nephrectomized kidneys of cancer patients: normotensive patients (NT) and patients with arterial hypertension (AH). LAs of patients with AH revealed endothelial dysfunction, which was associated with an increased response to the exogenous NO donor, nitrosoglutathione (GSNO). The interaction of GSNO with the H2S donor triggered a specific vasoactive response. Unlike in normotensive patients, in patients with AH, the starting and returning of the vasorelaxation induced by the end-products of the H2S-GSNO interaction (S/GSNO) was significantly faster, however, without the potentiation of the maximum. Moreover, increasing glycemia shortened the time required to reach 50% of the maximum vasorelaxant response induced by S/GSNO products so modulating their final effect. Moreover, we found out that, unlike K+ channel activation, cGMP pathway and HNO as probable mediator could be involved in mechanisms of S/GSNO action. For the first time, we demonstrated the expression of genes coding H2S-producing enzymes in perivascular adipose tissue and we showed the localization of these enzymes in LAs of normotensive patients and in patients with AH. Our study confirmed that the heterogeneity of specific nitroso-sulfide vasoactive signaling exists depending on the occurrence of hypertension associated with increased plasma glucose level. Endogenous H2S and the end-products of the H2S-GSNO interaction could represent prospective pharmacological targets to modulate the vasoactive properties of human intrarenal arteries.

Fructose Intake Impairs the Synergistic Vasomotor Manifestation of Nitric Oxide and Hydrogen Sulfide in Rat Aorta

“…Our previous studies showed an obvious interaction between two important vasoregulatory molecules, NO and H 2 S, and their pathways and suggested the existence of a coupled nitroso-sulfide signaling pathway [24,25]. Herein, we confirmed that the heterogeneity of specific nitroso-sulfide vasoactive signaling exists depending on the occurrence of different pathological stages, e.g., hypertension or increased plasma glucose levels [26]. Recently, in a non-obese rat model of metabolic syndrome (HTG rats), we confirmed a significantly higher expression of CSE in the arterial wall of the TA compared to control rats, and that the endogenous H 2 S participated in the inhibition of NO-mediated vasorelaxation [27].…”

“…Interestingly, it seems that there was a higher expression of CBS than in CSE in the aortic arterial wall (Figure 10). We previously found similar results in human intrarenal arteries, where we did not record gene expression of CSE in the arterial wall, but the mRNA of CBS was detectable [26]. This finding could explain the evidence that the acute inhibition of CSE revealed weaker vasoactive effects than the H 2 S scavenger, and BSC could eliminate H 2 S also produced by CSE-independent sources, including CBS.…”

Cardiovascular “Patterns” of H2S and SSNO−-Mix Evaluated from 35 Rat Hemodynamic Parameters

“…Several reports propose that the products of H 2 S-NO interaction, particularly SSNO − , play an important role in the regulation of BP [ 9 , 17 , 18 , 37 ]. Therefore, we have studied the effect of SSNO − -mix on BP.…”

“…Since endogenously produced gasotransmitters, hydrogen sulfide (H 2 S) and nitric oxide (NO), and the products of H 2 S/NO interactions (referred as SSNO − -mix) influence various physiological processes, particularly regulate blood pressure (BP) [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], it was of interest to study the effects of H 2 S and SSNO − -mix on 35 HPs and subsequently compare the selected cross-relationships of the HPs and their non-hysteresis/hysteresis “patterns” to the published data for NO-donor S-nitrosoglutathione (GSNO) [ 4 ].…”

Mechanisms Modified by (−)-Epicatechin and Taxifolin Relevant for the Treatment of Hypertension and Viral Infection: Knowledge from Preclinical Studies

“…Dysregulation of the cross-talk between EDRFs and EDCFs results in the alteration of normal physiological processes carried out by the endothelium, including reduction of its anticoagulant and antithrombotic properties, acceleration of vascular growth and remodeling, and impairment of endothelium-dependent vasorelaxation, i.e., in endothelial dysfunction [ 6 ]. Endothelial dysfunction was documented not only in animal models, but also in patients with arterial hypertension [ 166 ]. Prevention of endothelial dysfunction represents an important step in the prevention or mitigation of CVDs and hypertension.…”