1. The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.
- Author
-
Liang YF, You QX, Chen SY, Ni L, Meng XL, Gao JX, Ren YB, Song HJ, Su JL, Teng Y, Gu QY, Lv C, Yuan BY, Wang X, Zheng YT, and Zhang DD
- Subjects
- Animals, Male, Rats, Arterial Pressure drug effects, Disease Models, Animal, Enzyme Inhibitors pharmacology, Hydroxylamine pharmacology, MAP Kinase Signaling System drug effects, Norepinephrine metabolism, Oxidative Stress drug effects, Rats, Inbred Dahl, Hydrogen Sulfide metabolism, Hypertension chemically induced, Hypertension physiopathology, Hypertension metabolism, Paraventricular Hypothalamic Nucleus drug effects, Paraventricular Hypothalamic Nucleus metabolism, Paraventricular Hypothalamic Nucleus enzymology, Paraventricular Hypothalamic Nucleus physiopathology, Sodium Chloride, Dietary
- Abstract
Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (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 groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure 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 H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF