PMID- 36235829 OWN - NLM STAT- MEDLINE DCOM- 20221017 LR - 20221019 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 19 DP - 2022 Oct 7 TI - Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters. LID - 10.3390/nu14194177 [doi] LID - 4177 AB - BACKGROUND: The hypothalamic paraventricular nucleus (PVN) is an important nucleus in the brain that plays a key role in regulating sympathetic nerve activity (SNA) and blood pressure. Silent mating-type information regulation 2 homolog-1 (sirtuin1, SIRT1) not only protects cardiovascular function but also reduces inflammation and oxidative stress in the periphery. However, its role in the central regulation of hypertension remains unknown. It is hypothesized that SIRT1 activation by resveratrol may reduce SNA and lower blood pressure through the regulation of intracellular reactive oxygen species (ROS) and neurotransmitters in the PVN. METHODS: The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension in male Sprague-Dawley rats. Then, bilaterally injections of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 muL) or resveratrol (a SIRT1 agonist, 160 mumol/L, 0.4 muL) into rat PVN were performed for four weeks. RESULTS: PVN SIRT1 expression was lower in the hypertension group than the sham surgery (SHAM) group. Activated SIRT1 within the PVN lowered systolic blood pressure and plasma norepinephrine (NE) levels. It was found that PVN of 2K1C animals injected with resveratrol exhibited increased expression of SIRT1, copper-zinc superoxide dismutase (SOD1), and glutamic acid decarboxylase (GAD67), as well as decreased activity of nuclear factor-kappa B (NF-kappaB) p65 and NAD(P)H oxidase (NOX), particularly NOX4. Treatment with resveratrol also decreased expression of ROS and tyrosine hydroxylase (TH). CONCLUSION: Resveratrol within the PVN attenuates hypertension via the SIRT1/NF-kappaB pathway to decrease ROS and restore the balance of excitatory and inhibitory neurotransmitters. FAU - Qi, Jie AU - Qi J AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Fu, Li-Yan AU - Fu LY AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Liu, Kai-Li AU - Liu KL AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Li, Rui-Juan AU - Li RJ AD - Department of Infectious Diseases, The Second Affiliated Hospital, Air Force Military Medical University, Xi'an 710038, China. FAU - Qiao, Jin-An AU - Qiao JA AD - Institute of Pediatric Diseases, Xi'an Children's Hospital, Xi'an 710002, China. FAU - Yu, Xiao-Jing AU - Yu XJ AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Yu, Jia-Yue AU - Yu JY AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Li, Ying AU - Li Y AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Feng, Zhi-Peng AU - Feng ZP AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Yi, Qiu-Yue AU - Yi QY AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Jia, Hong AU - Jia H AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Gao, Hong-Li AU - Gao HL AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. FAU - Tan, Hong AU - Tan H AUID- ORCID: 0000-0002-8660-8222 AD - College of Life Sciences, Northwest University, Xi'an 710069, China. FAU - Kang, Yu-Ming AU - Kang YM AD - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Institute of Cardiovascular Sciences, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. AD - Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China. LA - eng GR - 82170451, 82070440, 82070439, 81500313/National Natural Science Foundation of China/ GR - 2020A02/Research Program of Xi'an Children's Hospital/ PT - Journal Article DEP - 20221007 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (NF-kappa B) RN - 0 (Neurotransmitter Agents) RN - 0 (Reactive Oxygen Species) RN - 789U1901C5 (Copper) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 1.15.1.1 (Superoxide Dismutase-1) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - J41CSQ7QDS (Zinc) RN - Q369O8926L (Resveratrol) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Animals MH - Copper/metabolism MH - Glutamate Decarboxylase/metabolism MH - *Hypertension MH - Male MH - NADPH Oxidases/metabolism MH - NF-kappa B/metabolism MH - Neurotransmitter Agents/metabolism MH - Norepinephrine/metabolism MH - *Paraventricular Hypothalamic Nucleus/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Resveratrol/metabolism/pharmacology MH - Sirtuin 1/genetics/metabolism MH - Superoxide Dismutase-1/metabolism MH - Sympathetic Nervous System/metabolism MH - Tyrosine 3-Monooxygenase/metabolism MH - Zinc/metabolism PMC - PMC9573276 OTO - NOTNLM OT - PVN OT - ROS OT - SIRT1 OT - excitatory and inhibitory neurotransmitters OT - high blood pressure OT - resveratrol COIS- The authors declare no conflict of interest. EDAT- 2022/10/15 06:00 MHDA- 2022/10/18 06:00 PMCR- 2022/10/07 CRDT- 2022/10/14 02:32 PHST- 2022/08/03 00:00 [received] PHST- 2022/09/24 00:00 [revised] PHST- 2022/09/30 00:00 [accepted] PHST- 2022/10/14 02:32 [entrez] PHST- 2022/10/15 06:00 [pubmed] PHST- 2022/10/18 06:00 [medline] PHST- 2022/10/07 00:00 [pmc-release] AID - nu14194177 [pii] AID - nutrients-14-04177 [pii] AID - 10.3390/nu14194177 [doi] PST - epublish SO - Nutrients. 2022 Oct 7;14(19):4177. doi: 10.3390/nu14194177.