Exogenous H2S Ameliorates High Salt-Induced Hypertension by Alleviating Oxidative Stress and Inflammation in the Paraventricular Nucleus in Dahl S Rats

Yingying Liao,Yuanyuan Fan,Enshe Jiang,Qinglin He,Yuwei Li,Dongdong Wu

doi:10.1007/s12012-022-09729-7

Abstract

Hydrogen sulfide (H2S) is an important gaseous signaling molecule that regulates cardiovascular activity in animals. The hypothalamic paraventricular nucleus (PVN) is a major integrative region involved in blood pressure (BP) regulation. We explored whether exogenous H2S application by intraperitoneal injection of sodium hydrosulfide (NaHS) alleviates BP increase induced by a high salt diet (HSD) and the role of PVN in Dahl salt-sensitive (Dahl S) rats. Dahl S rats were divided into four groups according to diet regime (normal salt diet [NSD] and HSD) and treatment method (daily intraperitoneal NaHS or saline injection). We monitored BP, food and water intake, and body weight for 8 weeks. Plasma, kidney, and brain tissues were collected at the end of the experiment. We found that exogenous H2S not only delayed BP elevation but also attenuated the increase in the levels of norepinephrine, cystatin C, and blood urea nitrogen in the plasma of Dahl S rats with an HSD. Furthermore, H2S enhanced the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in the PVN. Exogenous H2S attenuated the protein expression of the nuclear factor-κB pathway and proinflammatory cytokines, which were significantly higher in the PVN in rats with an HSD than in rats with an NSD. Additionally, exogenous H2S relieved PVN neuronal apoptosis induced by an HSD. These findings suggest that exogenous H2S attenuates hypertension caused by an HSD by ameliorating oxidative stress, inflammation, and apoptosis in the PVN. This study provides evidence of the benefits of peripheral H2S therapy for hypertension.

Highlights

Hypertension is a type of cardiovascular and cerebrovascular disease that is characterized by a continuous elevation of blood pressure (BP) that results in associated seriousHandling Editor: Y
The present study produced three key findings: (i) exogenous H2S application by intraperitoneal injection delayed the high salt diet (HSD)-induced BP increase in Dahl salt-sensitive (Dahl S) rats by alleviating peripheral tissue damage in the heart and kidneys; (ii) exogenous H2S application attenuated oxidative stress, protein expression of the NF-κB pathway, and production of proinflammatory cytokines (PICs) in the paraventricular nucleus (PVN) of Dahl S rats; and (iii) exogenous H 2S application reduced cell apoptosis of the PVN induced by an HSD in Dahl S rats
Similar to other bio-gaseous molecules, such as carbon monoxide (CO) and nitric oxide (NO), H2S has been considered as a novel molecule that can be used to treat high BP and kidney damage caused by an high-fat diet (HFD) [13, 20]

Summary

Introduction

Hypertension is a type of cardiovascular and cerebrovascular disease that is characterized by a continuous elevation of blood pressure (BP) that results in associated serious. Yingying Liao and Yuanyuan Fan contributed to this work. It is well established that the hypothalamic paraventricular nucleus (PVN) is an important nucleus for the central regulation of cardiovascular activity. It contains rich autonomic neurons that participate in the regulation of sympathetic nerve activity and BP [3, 4]. Neuronal activation of the PVN can increase the neuro-excitatory response, raise BP, and increase heart rate under conditions of stress [3, 4]

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