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논문분류	춘계학술대회 초록집
제목	HDAC8 inhibition ameliorates hypertension by inhibiting sympathetic nervous system and angiotensin II
저자	Gwan Beom Lee
출판정보	2024; 2024(1):
키워드
초록	Objectives: Obesity is one of the major diseases that increase the incidence of metabolic syndrome and complications such as hyperlipidemia, chronic kidney disease, cardiovascular disease, as well as hypertension. Obesity increases the activity of sympathetic nerve system (SNS) and renin-angiotensin (RAS) causing hypertension through vasoconstriction and increased water reabsorption. Histone deacetylases (HDACs) regulate gene expression and are known to play an important role in cardiovascular diseases, including hypertension. However, the role of HDAC8 in the upregulation of renal SNS and angiotensin II (AngII) in obesity-mediated hypertension is unknown. In this study, we determined the effect of selective HDAC8 inhibitor, on high-fat diet-induced hypertension through regulating high-fat diet renal SNS and AngII. Methods: Nine-week-old male C57BL/6 mice were fed a normal diet normal diet (ND) or high-fat diet (HFD) for 16 weeks. When the HFD group reached the hypertensive phase, each group of mice was administered with vehicle or the HDAC8 inhibitor for 16 days (0.5mg kg-1 per day). Results: HFD raised BP and increased HDAC8 activity in the kidney. HDAC8 inhibition canceled increased HDAC8 activity in the kidney with the amelioration of hypertension. Urine dopamine, norepinephrine (NE), and epinephrine(EPI) were increased by HFD but only NE and EPI were reversed by HDAC8 inhibition. Expression of dopamine beta-hydroxylase (DBH), which converts dopamine to NE was unaffected by HFD. Phenylethanolamine N-methyltransferase (PNMT), which converts NE to EPI was increased by HFD and reversed by HDAC8 inhibition. Kidney angiotensinogen (Agt) expression and AngII level were increased by HFD and reversed by HDAC8 inhibition. Enhanced expression of various sodium transporters and inflammatory cytokines by HFD were reversed by HDAC8 inhibition. Conclusions: In conclusion, HDAC8 inhibition ameliorates obesity hypertension through inhibition of renal SNS and AngII. Providing HDAC8 inhibitor as a therapeutic option for obesity hypertension.
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