title: Characterization of imidazoline receptors in blood vessels for the development of antihypertensive agents.
abstract: It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to open KATP channels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Neipu, Pingtung 91201, Taiwan ; College of Medicine and Life Science, Chung Hwa University of Medical Technology, Rende District, Tainan City 71703, Taiwan.
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Taipei Medical University-Shuang Ho Hospital, and College of Medicine, Taipei Medical University, Taipei City 10361, Taiwan.
authors.forename: Jo-Ting
authors.identifier: 0000-0001-7745-1131
authors.initials: JT
authors.lastname: Tsai
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Obs/Gyn, Tainan Sin-Lau Hospital, The Presbyterian Church in Taiwan, Tainan City 70142, Taiwan.
authors.forename: Tung-Pi
authors.initials: TP
authors.lastname: Wu
authors.affiliation: College of Medicine and Life Science, Chung Hwa University of Medical Technology, Rende District, Tainan City 71703, Taiwan.
authors.forename: Jia-Jang
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: College of Medicine and Life Science, Chung Hwa University of Medical Technology, Rende District, Tainan City 71703, Taiwan.
authors.forename: Li-Te
authors.initials: LT
authors.lastname: Yin
authors.affiliation: College of Medicine and Life Science, Chung Hwa University of Medical Technology, Rende District, Tainan City 71703, Taiwan.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Yang
authors.affiliation: College of Medicine and Life Science, Chung Hwa University of Medical Technology, Rende District, Tainan City 71703, Taiwan.
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chiang
authors.affiliation: Department of Chinese Medicine, Tainan Sin-Lau Hospital, The Presbyterian Church in Taiwan, Tainan City 70142, Taiwan.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Lu
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology, Neipu, Pingtung 91201, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D019791:Guanidine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D054755:Imidazoline Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D019791:Guanidine