The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt–Induced Hypertension

Abstract

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.