Hydrogen Sulfide Inhibited Sympathetic Activation in D-Galactose-Induced Aging Rats by Upregulating Klotho and Inhibiting Inflammation in the Paraventricular Nucleus

Author:

Yu Hao1,Yu Qiyao12,Mi Yuan13,Wang Ping1,Jin Sheng1,Xiao Lin1,Guo Qi14,Wu Yuming156

Affiliation:

1. Department of Physiology, Institute of Basic Medicine, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang 050017, China

2. Department of Research, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China

3. Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China

4. Experimental Center for Teaching, Hebei Medical University, Shijiazhuang 050017, China

5. Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang 050017, China

6. Key Laboratory of Vascular Medicine of Hebei Province, Shijiazhuang 050017, China

Abstract

The present study aimed to explore the central relationship between cardiovascular conditions and aging. D-galactose (D-gal) was utilized to induce an accelerated aging model and to evaluate the effects of hydrogen sulfide (H2S) on aging-related cardiovascular risk factors and mechanisms. Eight-week-old Sprague Dawley rats were given an intraperitoneal injection of 250 mg/kg D-gal every day with or without H2S (56 μmol/kg) for 12 weeks. We found that D-gal treatment induced a noticeably aging-related increase in p16, p53 and p21 protein levels and senescence-associated beta-galactosidase staining. In addition, the level of noradrenalin was increased, accompanied by enhanced blood pressure and renal sympathetic nerve activity in aged rats. The greater sympathetic responses were related with the increased level of inflammation. The decreased level of klotho in the paraventricular nucleus neuron also contributed to sympathetic activation in D-gal-induced aged rats. However, the exogenous administration of H2S attenuated the sympathetic activity in aged rats, as evidenced by the decreased blood pressure, renal sympathetic nerve activity and noradrenalin level. The ameliorated cellular senescence, inflammation and heightened klotho in the paraventricular nucleus were attributed to the protective effects of H2S. The present study provides further evidence for the drug development of H2S for the prevention or treatment of the aging-associated cardiovascular diseases.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Hebei Province of China

Youth Top Talent Program Foundation of Hebei Province of China

Key S&T Program of Hebei

Science and Technology Project of the Hebei Education Department

Scientific Research Foundation of Hebei Province for the Returned Overseas Chinese Scholars

Program of Clinical Medicine Innovation Research Team of Hebei Medical University

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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