title: Farnesoid X receptor agonist CDCA reduces blood pressure and regulates vascular tone in spontaneously hypertensive rats.
abstract: The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, which plays an essential role in lipid homeostasis and glucose metabolism. However, whether or not FXR can prevent rise in blood pressure remains unknown. Here, we investigate the possibility of using chenodeoxycholic acid (CDCA), a natural ligand of FXR, to attenuate elevated blood pressure in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were treated with CDCA (30 mg/kg) for 8 weeks. Compared with vehicle control, CDCA attenuated rise in blood pressure in SHR. In addition, CDCA improved vasorelaxation and diminished the contractile response to endothelin-1 (ET-1) in mesenteric arteries from SHR. CDCA also stimulated endothelial nitric oxide synthase (eNOS) expression, repressed ET-1 levels, and inhibited NF-κB activities in mesenteric arteries of the SHR. Overall, we showed that CDCA treatment reduces systolic blood pressure, improves vascular relaxation, and inhibits vasoconstriction activity in SHR. The repressed ET-1 level, the raised eNOS expression, and the ameliorated inflammation in mesenteric arteries could be responsible for the vasorelaxant and hypotensive effect of CDCA. These findings support a potential role for FXR as a regulator in vascular activities and in the development of treatment for hypertension.
authors.affiliation: Department of Neurology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Neurology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Internal Medicine, Qijiang People's Hospital, Qijiang, Chongqing, China. Electronic address: xiangbochi@163.com.
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Chi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D008638:Mesenteric Arteries / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000959:Antihypertensive Agents; D002635:Chenodeoxycholic Acid; D019332:Endothelin-1; D016328:NF-kappa B; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D019010:Vascular Cell Adhesion Molecule-1; D000099150:Receptor, Farnesoid X-Activated
keywords: Bile Acid; hypertension; inflammation; nitric oxide; nuclear receptor