Zhou Nan, Wang Tao, Song Jia, He Huaizhen, He Jianyu, He Langchong
School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Clin Exp Pharmacol Physiol. 2014 Aug;41(8):571-8. doi: 10.1111/1440-1681.12248.
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.
OW1是一种具有血管舒张活性的新型欧前胡素衍生物。在本研究中，我们在二肾一夹（2K1C）肾血管性高血压大鼠中研究了OW1的降压作用及其对血管重塑的抑制作用。大鼠接受2K1C手术，并给予OW1（每天40或80mg/kg）治疗8周。在清醒大鼠中测量血压。测定尿液中的微量白蛋白（mALB）和总蛋白（U-TP）浓度，以及血浆中血管紧张素（Ang）II、降钙素基因相关肽（CGRP）和血管紧张素转换酶1（ACE）的浓度。未夹闭的肾脏用苏木精和伊红以及Masson三色染色，而主动脉切片用Masson三色染色。此外，在体外评估了OW1对大鼠肠系膜动脉和肾动脉的舒张作用。采用免疫组织化学分析对I型和III型胶原蛋白表达进行定量。OW1在体外使大鼠肠系膜动脉和肾动脉环舒张。用OW1（每天40和80mg/kg）治疗2K1C高血压大鼠8周可显著降低血压。此外，OW1降低了血浆AngII和ACE浓度，并增加了血浆CGRP浓度。在每天80mg/kg时，OW1降低了血尿素氮、mALB和U-TP水平。组织学分析显示，OW1降低了肾小动脉厚度，缓解了动脉结构肥厚。此外，OW1对高血压大鼠的血管重塑和肾脏病变具有抑制作用。总之，结果表明OW1可能是一种新型的高血压干预候选药物。
