Hydrogen sulfide in the paraventricular nucleus attenuates endoplasmic reticulum stress in Spontaneous hypertension

Hydrogen sulfide (H₂S), known as a metabolic modulator, is a gaseous signaling molecule with functions similar to those of nitric oxide and carbon monoxide, all of which possess vasodilatory, antioxidant, and other properties. In the central nervous system, H₂S is a signaling molecule that is crucial for neuroprotection and the control of neurological processes. The paraventricular nucleus (PVN) of the hypothalamus is an important central nucleus that regulates and integrates cardiovascular and peripheral sympathetic activity. This study aimed to investigate whether intra-PVN injection of the endogenous H₂S synthase CBS activator S-adenosylmethionine (SAMe) or the endogenous H₂S synthase CBS inhibitor hydroxylamine (HA) modulates H₂S expression in the PVN, whether microglia in the PVN are targeted by H₂S, and whether PVN H₂S further induces alterations in blood pressure(BP) by affecting endoplasmic reticulum(ER) stress in the PVN of spontaneously hypertensive rats (SHR). Healthy male Wistar-Kyoto (WKY) rats and SHR were fed a normal diet for 8 weeks, followed by intra-PVN injections of SAMe, HA, or vehicle for 4 weeks. Plasma norepinephrine levels and mean arterial pressure were elevated in the SHR group. The expression of factors related to ER stress, such as p-PERK, GRP78, and p-IRE1α, was also elevated. Levels of these parameters were lower in the SHR + SAMe group, whereas the SHR + HA group presented with higher levels of these indicators. These findings suggest that endogenous H₂S attenuates sympathetic activity and hypertensive responses in the PVN, in part by modulating ER stress.