期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 300, 期 6, 页码 R1468-R1475出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00215.2010
关键词
renovascular hypertension; cytochrome P-450 metabolites; epoxyeicosatrienoic acids; hydroxyeicosatrienoic acids; renal functions; blood pressure autoregulation; glomerular filtration rate; renal blood flow; cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid; HET-0016
类别
资金
- EU [CZ.2.16/3.1.00/22126]
- European Commission [IRG 247847]
- Czech Science Foundation (GACR) [303/10/P170]
- GACR [305/08/J006]
- Internal Grant Agency of the Ministry of Health of the Czech [NS/10499-3]
- Institute for Clinical and Experimental Medicine [MZO 00023001]
- Internal Grant Agency of the Ministry of Health of the Czech Republic
- Grant Agency of the Academy of Science of Czech Republic [KJB 502030801]
- National Institutes of Health [HL-59699, DK-38226]
- Advancing a Healthier Wisconsin
- German Research Foundation (DFG), Bonn [Kra 433/14-2, 436 TSE 113/50/0-1]
- Howard Hughes Foundation
- National Institute of Environmental Health Sciences (NIEHS) [R37 ES-02710, P42 ES-004699]
Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 +/- 1 vs. 163 +/- 3 mmHg) and increased sodium excretion (1.23 +/- 0.10 vs. 0.59 +/- 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 +/- 0.2 vs. 6.9 +/- 0.2 ml.min(-1).g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 +/- 0.6 ml.min(-1).g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 +/- 0.2 ml.min(-1).g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据