title: Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas.
abstract: Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper contaminated soil in China, which has been reported to benefit cardiovascular systems as folk medicine. However, few direct evidences have been found to clarify the vasorelaxation effect of total flavonoids of ES (TFES). The vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFES (5-200mg/L) caused a concentration-dependent vasorelaxation in endothelium-intact rings, which was not abolished but significantly reduced by the removal of endothelium. The nitric oxide synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (100μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (30μM) significantly blocked the endothelium-dependent vasorelaxation of TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration-dependently elevated by TFES. However, indomethacin (10μM) did not affect TFES-induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was significantly attenuated by KATP channel blocker glibenclamide. The accumulative Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or phenylephrine was markedly weakened by TFES. These results revealed that the NOS/NO/cGMP pathway is likely involved in the endothelium-dependent vasorelaxation induced by TFES, while activating KATP channel, inhibiting intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+) influx into vascular smooth muscle cells might contribute to the endothelium-independent vasorelaxation conferred by TFES.
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Lu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Xu-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Peng
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Ye
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.affiliation: Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Physiology, Zhejiang Medical College, Hangzhou 310053, PR China. Electronic address: bioqian@163.com.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Qian
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002681:China; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D064028:Tracheophyta / Q000737:chemistry*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D007213:Indomethacin
keywords: Aorta; Calcium channels; Endothelium; Potassium channels; Total flavonoids of Elsholtzia splendens; Vasorelaxation