Antihypertensive and vascular remodelling effects of the imperatorin derivative OW1 in renovascular hypertension rats

摘要

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.