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

Hydrogen sulfide (HS) 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 HS 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 HS 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, HS enhanced the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in the PVN. Exogenous HS 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 HS relieved PVN neuronal apoptosis induced by an HSD. These findings suggest that exogenous HS 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 HS therapy for hypertension.