Exogenous H 2 S Ameliorates High Salt-Induced Hypertension by Alleviating Oxidative Stress and Inflammation in the Paraventricular Nucleus in Dahl S Rats.

Hydrogen sulfide (H 2 S) 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 H 2 S 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 H 2 S 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, H 2 S enhanced the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in the PVN. Exogenous H 2 S 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 H 2 S relieved PVN neuronal apoptosis induced by an HSD. These findings suggest that exogenous H 2 S 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 H 2 S therapy for hypertension.