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

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.

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters

“…Researchers have also found that NF-κB activities in the PVN are closely associated with the intensity of SNA in hypertensive rats [ 24 , 47 ]. NF-κB and oxidative stress in PVN play crucial roles in the pathogenesis of hypertension [ 38 , 48 ].…”

“…The activity of NF-κB in the PVN is closely related to the enhancement of SNA. Inhibiting NF-κB activities greatly reduced ROS and SNA in hypertension [ 24 ] and myocardial infarction rat models [ 25 , 26 ]. The authors of [ 27 ] found that NF-κB activity increased in myeloid-specific SIRT1 knockout mice, suggesting that SIRT1 in bone marrow may inhibit NF-κB activation.…”

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

“…This study used HE staining to observe the effects of long-term high salt diet on the structure of the heart and arteries in rats. The process of HE staining was performed as previously described ( Liao et al, 2022 ).…”

Pathophysiological Association of Alzheimer’s Disease and Hypertension: A Clinical Concern for Elderly Population

“…For example, chronic neuroinflammation in the paraventricular nucleus of the hypothalamus induced by long-term high salt intake could lead to HTN in the Dahl salt-sensitive rat model. 118 , 119 On another side, HTN could also induce microvascular inflammation in the brain. So, cerebral microvascular inflammation likely accelerated cognitive impairment in the elderly with AD under HTN.…”