title: Changes of imidazoline receptors in spontaneously hypertensive rats.
abstract: The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar-Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I(2) -receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I(1) -receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (K(ATP) ) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I(2) -receptor, which is expressed more highly in SHRs.
authors.affiliation: Department of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Mar
authors.forename: Ming-Ting
authors.initials: MT
authors.lastname: Chou
authors.forename: Hsien-Hui
authors.initials: HH
authors.lastname: Chung
authors.forename: Nien-Hua
authors.initials: NH
authors.lastname: Chiu
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015153:Blotting, Western; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000819:agonists* / Q000378:metabolism; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; C105826:BU 224; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; C487767:imidazoline receptor 2; D000376:Agmatine; D017868:Cyclic AMP-Dependent Protein Kinases; C062597:efaroxan