title: Antihypertensive and vascular remodelling effects of the imperatorin derivative OW1 in renovascular hypertension rats.
abstract: OW1 is a novel imperatorin derivative that exhibits vasodilator activity. In the present study, the antihypertensive effect of and inhibition of vascular remodelling by OW1 were investigated in two-kidney, one-clip (2K1C) renovascular hypertensive rats. Rats were subjected to the 2K1C procedure and treated with OW1 (40 or 80 mg/kg per day) for 8 weeks. Blood pressure was measured in conscious rats. Microalbumin (mALB) and total protein (U-TP) concentrations were determined in the urine, as were plasma concentrations of angiotensin (Ang) II, calcitonin gene-related peptide (CGRP) and angiotensin-converting enzyme 1 (ACE). The unclipped kidney was stained with haematoxylin and eosin and Masson trichrome, whereas aortic sections were stained with Masson trichrome. In addition, OW1-induced vasodilatation was evaluated in vitro in rat mesenteric and renal arteries. Immunohistochemical analysis was used to quantify collagen I and III expression. OW1 relaxed rat mesenteric and renal arterial rings in vitro. Treatment of 2K1C hypertensive rats with OW1 (40 and 80 mg/kg per day) for 8 weeks significantly decreased blood pressure. In addition, OW1 reduced plasma AngII and ACE concentrations and increased plasma CGRP concentrations. At 80 mg/kg per day, OW1 decreased blood urea nitrogen, mALB and U-TP levels. Histological analysis revealed that OW1 reduced renal arteriolar thickness and relieved the structural hypertrophic arteries. Moreover, OW1 had an inhibitory effect on vascular remodelling and renal lesions in hypertensive rats. In conclusion, the results suggest that OW1 could potentially be a novel candidate for hypertension intervention.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Huaizhen
authors.initials: H
authors.lastname: He
authors.forename: Jianyu
authors.initials: J
authors.lastname: He
authors.forename: Langchong
authors.initials: L
authors.lastname: He
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D011564:Furocoumarins / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D024042:Collagen Type I; D024061:Collagen Type III; D011564:Furocoumarins; D014665:Vasodilator Agents; D000804:Angiotensin II; D015740:Calcitonin Gene-Related Peptide; C031534:imperatorin
keywords: angiotensin II; blood pressure; collagen I; collagen III; imperatorin derivative OW1; one-clip hypertensive rats; two-kidney