title: Andrographolide protects against lipopolysaccharide-induced vascular hyporeactivity by suppressing the expression of inducible nitric oxide in periaortic adipose.
abstract: This study investigated the role of perivascular adipose tissue (PVAT) in the beneficial effects of andrographolide on vascular reactivity in endotoxaemic rats. After being challenged by lipopolysaccharide (4 mg/kg intraperitoneally), the rats were treated with andrographolide (1 mg/kg intraperitoneally). The response to phenylephrine of aortic rings with or without PVAT was recorded. Vascular relaxing effect of PVAT was determined by bioassay experiments. Inducible nitric oxide synthase (iNOS) in aortic PVAT was tested by Western blot, immunofluorescence, and quantitative polymerase chain reaction. Lipopolysaccharide injection lowered the contraction force induced by phenylephrine in aortic rings with or without PVAT and andrographolide treatment reversed these effects. In bioassay experiments, transferring bathing solution incubated with a PVAT+ ring to a PVAT- ring induced relaxation in the recipient. This relaxing effect of PVAT from endotoxaemic rats was more potent than the rats treated with vehicles. Andrographolide treatment decreased the relaxing effect of PVAT in endotoxaemic rats. The levels of iNOS protein and messenger RNA in PVAT were significantly higher in endotoxaemic rats than in the rats treated with vehicles. Andrographolide treatment decreased PVAT iNOS protein and messenger RNA levels in endotoxaemic rats. Our results suggest that andrographolide restores vascular reactivity in endotoxaemic rats by downregulation of iNOS in PVAT.
authors.affiliation: Department of Physiology, Basic Medical College, Guangzhou University of Chinese Medicine, University Town, Guangzhou, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hai-Mei
authors.forename: Huang
authors.initials: H
authors.lastname: Song-Yin
authors.forename: Li
authors.initials: L
authors.lastname: Run-Mei
authors.forename: Xu
authors.initials: X
authors.lastname: Xiao-Huang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Le-Quan
authors.forename: Lai
authors.initials: L
authors.lastname: Xiao-Ping
authors.forename: Xu
authors.initials: X
authors.lastname: Jin-Wen
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects*; D004351:Drug Resistance / Q000187:drug effects; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000209:etiology / Q000517:prevention & control; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C030419:andrographolide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat