title: Tetrahydroxystilbene Glucoside Inhibits Excessive Autophagy and Improves Microvascular Endothelial Dysfunction in Prehypertensive Spontaneously Hypertensive Rats.
abstract: Autophagy exists in vascular endothelial cells, but the relationship between autophagy and blood vessel dysfunction in hypertension remains elusive. This study aimed to investigate role of autophagy in vascular endothelial dysfunction in prehypertension and hypertension and the underlying mechanisms involved. Furthermore, we sought to determine if and how tetrahydroxystilbene glucoside (TSG), a resveratrol analogue and active ingredient of Polygonum multiflorum Thunb used for its cardiovascular protective properties in traditional Chinese medicine, influences vascular endothelial function. Male spontaneously hypertensive rats (SHRs) aged 4 weeks (young) and 12 weeks (adult) were studied and the vascular function of isolated aorta and mesenteric artery was assessed in vitro. Compared with Wistar Kyoto rats (WKY), young and adult SHRs showed endothelial dysfunction of the aorta and mesenteric artery, along with decreased pAkt, pmTOR, and autophagic marker protein p62 and increased LC3 II/I in microvascular but not aortic tissues. TSG administration for 14 days significantly improved mesenteric vascular endothelial function, increased levels of pAkt and pmTOR, and decreased autophagy. Pretreatment of young SHRs with the mTOR inhibitor rapamycin blocked the antiautophagic and vasodilative effects of TSG. Moreover, TSG significantly activated Akt-mTOR signaling in HUVECs and reduced the autophagic levels in vitro, which were almost completely blocked by rapamycin. In summary, mesenteric endothelial dysfunction in prehypertensive SHRs was at least partly attributable to excessive autophagy in vascular tissues. TSG partly restored microvascular endothelial dysfunction through activating the Akt/mTOR pathway, which consequently suppressed autophagy, indicating that TSG could be potentially applied to protect vascular function against subclinical changes in prehypertension.
authors: * Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Qianqian
authors: Q
authors: Dong
authors: † Department of Physiology, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Wenjuan
authors: W
authors: Xing
authors: † Department of Physiology, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Feng
authors: F
authors: Fu
authors: † Department of Physiology, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Zhenghua
authors: Z
authors: Liu
authors: ‡ Experiment Teaching Center, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Jie
authors: J
authors: Wang
authors: ‡ Experiment Teaching Center, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Xiangyan
authors: X
authors: Liang
authors: * Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Xuanxuan
authors: X
authors: Zhou
authors: * Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Qian
authors: Q
authors: Yang
authors: § Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Wei
authors: W
authors: Zhang
authors: † Department of Physiology, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Feng
authors: F
authors: Gao
authors: * Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Siwang
authors: S
authors: Wang
authors: ‡ Experiment Teaching Center, Fourth Military Medical University, Xi'an 710032, P.R. China.
authors: Haifeng
authors: H
authors: Zhang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D000068676:Fallopia multiflora / Q000737:chemistry*; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D055806:Microvessels / Q000166:cytology; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014665:Vasodilator Agents
chemical_list: C489707:2',3',4',5'-tetrahydroxystilbene-2-O-beta-D-glucoside; D005960:Glucosides; D013267:Stilbenes; D014665:Vasodilator Agents; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: 2,3,5,4′-tetrahydroxystilbene-2-O--D-glucoside; Autophagy; Mesenteric Arteries; Prehypertension; Vascular Endothelial Dysfunction