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

doi:10.12307/2023.188

Abstract

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

CLC Number:

Zhang Dongdong, Gu Qingyun, You Qingxin, Jin Yingxin, Zhang Jiani, Wang Haoran, Wang Fengyue, Chen Shuyue, Su Jialu, Liang Yanfeng. Effects of hydrogen sulfide in paraventricular nuclei on PI3K/Akt pathway and blood pressure in high salt-induced hypertensive rats[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(26): 4168-4174.

Figures/Tables 7

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