2023, Vol. 27 ›› Issue (26): 4168-4174

Effects of hydrogen sulfide in paraventricular nuclei on PI3K/Akt pathway and blood pressure in high salt-induced hypertensive rats

Zhang Dongdong1, 2, Gu Qingyun1, 2, You Qingxin1, 2, Jin Yingxin1, 2, Zhang Jiani1, 2, Wang Haoran1, 2, Wang Fengyue1, 2, Chen Shuyue1, 2, Su Jialu1, 2, Liang Yanfeng1, 2#br#   

Abstract: BACKGROUND: The paraventricular nucleus is the center of cardiovascular regulation, which plays an important role in the regulation of peripheral sympathetic nerves and blood pressure. As a new type of gas signal molecular, hydrogen sulfide has anti-inflammatory and anti-oxidation effects. And the synthetase of hydrogen sulfide is expressed in the paraventricular nucleus. The mechanism of hydrogen sulfide in hypertension needs to be studied.
OBJECTIVE: To study the effects of hydrogen sulfide in the paraventricular nucleus on blood pressure, peripheral sympathetic nerve activity and PI3K/Akt pathway in high salt-induced hypertensive rats and to explore the mechanism of hydrogen sulfide in hypertension.
METHODS: Forty male Dahl rats were randomly divided into four groups: normal control group, normal intervention group, high-salt model group and high-salt intervention group. The rats in the two high-salt groups were fed high-salt diet for 4 weeks. The blood pressure of each rat was monitored by the caudal artery every week. After 4 weeks, the rats in the intervention groups were injected with GYY4137 in the bilateral paraventricular hypothalamic nucleus through a micro osmotic pump. Rats in the normal control group and the high-salt model group were given the same amount of artificial cerebrospinal fluid. After 6 weeks, the levels of plasma norepinephrine and hydrogen sulfide in the paraventricular nucleus were detected by ELISA, and the expressions of PI3K-p85, p-Akt and t-Akt in the paraventricular nucleus were detected by western blot and immunohistochemistry.
RESULTS AND CONCLUSION: Compared with the normal control group, the levels of mean arterial pressure and plasma norepinephrine were significantly increased in the high-salt model group (P < 0.01). Compared with the high-salt model group, the levels of mean arterial pressure and plasma norepinephrine were significantly decreased in the high-salt intervention group (P < 0.01). Compared with the normal control group, the expressions of PI3K-P85 and p-Akt in the paraventricular nucleus were significantly increased in the high-salt model group (P < 0.01). Compared with the high-salt model group, the expressions of PI3K-P85 and p-Akt were significantly decreased in the high-salt intervention group (P < 0.01). These results suggest that hydrogen sulfide in the paraventricular nucleus can inhibit the peripheral sympathetic nerve activity and lower the blood pressure after high salt-induced hypertension. When the blood pressure is decreased by hydrogen sulfide, the PI3K/Akt pathway in the paraventricular nucleus can be significantly inhibited, which will lay a theoretical foundation for finding new targets and developing new drugs for the clinical treatment of hypertension.

Key words: hydrogen sulfide, hypertension, paraventricular nucleus, PI3K/Akt pathway, norepinephrine, model, rat