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.
Highlights
H2 S is an important gaseous mediator that is presumed to control blood pressure by the direct regulation of vascular tone
The novel finding of the present study is that the heterogeneity of the vasoactive effects of specific nitroso-sulfide signaling in patients exists depending on the occurrence of hypertension associated with increased plasma glucose levels
In the conditions of arterial hypertension, using renal arteries isolated from spontaneously hypertensive rats (SHR) we found out that the pre-treatment with ODQ, inhibitor of soluble guanylate cyclase, significantly inhibited the vasorelaxant effect induced by the S-GSNO interaction (S/GSNO)
Summary
H2 S is an important gaseous mediator that is presumed to control blood pressure by the direct regulation of vascular tone. A deficiency in the H2 S signaling pathway plays an important role in the development of certain cardiovascular complications, such as spontaneous hypertension, atherosclerosis, heart failure and diabetes [1,2,3,4]. In a rat model of streptozotocin-induced diabetes, the authors found a decreased H2 S concentration in response to high glucose and confirmed that treatment with an H2 S donor significantly reverses the proliferation of smooth muscle cells caused by hyperglycemia. A high concentration of glucose causes a decrease in intracellular glutathione (GSH) [5]. GSH represents a significant part of the cellular antioxidant defense system that could play an important role in maintaining blood pressure in patients with hypertension
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