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Antihypertensive and vascular remodelling effects of the imperatorin derivative OW 1 in renovascular hypertension rats
Author(s) -
Zhou Nan,
Wang Tao,
Song Jia,
He Huaizhen,
He Jianyu,
He Langchong
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12248
Subject(s) - masson's trichrome stain , endocrinology , medicine , renovascular hypertension , calcitonin gene related peptide , kidney , blood pressure , angiotensin ii , renal function , mesenteric arteries , renal artery , vasodilation , chemistry , artery , immunohistochemistry , neuropeptide , receptor
Summary OW 1 is a novel imperatorin derivative that exhibits vasodilator activity. In the present study, the antihypertensive effect of and inhibition of vascular remodelling by OW 1 were investigated in two‐kidney, one‐clip (2 K 1 C ) renovascular hypertensive rats. Rats were subjected to the 2 K 1 C procedure and treated with OW 1 (40 or 80 mg/kg per day) for 8 weeks. Blood pressure was measured in conscious rats. Microalbumin (m ALB ) and total protein ( U ‐ TP ) concentrations were determined in the urine, as were plasma concentrations of angiotensin ( A ng) 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, OW 1‐induced vasodilatation was evaluated in vitro in rat mesenteric and renal arteries. Immunohistochemical analysis was used to quantify collagen I and III expression. OW 1 relaxed rat mesenteric and renal arterial rings in vitro . Treatment of 2 K 1 C hypertensive rats with OW 1 (40 and 80 mg/kg per day) for 8 weeks significantly decreased blood pressure. In addition, OW 1 reduced plasma A ng II and ACE concentrations and increased plasma CGRP concentrations. At 80 mg/kg per day, OW 1 decreased blood urea nitrogen, m ALB and U ‐ TP levels. Histological analysis revealed that OW 1 reduced renal arteriolar thickness and relieved the structural hypertrophic arteries. Moreover, OW 1 had an inhibitory effect on vascular remodelling and renal lesions in hypertensive rats. In conclusion, the results suggest that OW 1 could potentially be a novel candidate for hypertension intervention.