Interactive effects of superoxide anion and nitric oxide on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension

Author:

Patterson Matthew E.,Mouton Cynthia R.,Mullins John J.,Mitchell Kenneth D.

Abstract

Superoxide anion contributes to the pathogenesis of various forms of hypertension, but its role in the development of malignant hypertension remains unclear. The present study was performed to determine the influence of superoxide anion on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Malignant hypertension was induced in male Cyp1a1-Ren2 rats ( n = 6) through dietary administration of the aryl hydrocarbon, indole-3-carbinol (0.3%) for 7–9 days. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats before and during intravenous infusion of the superoxide dismutase mimetic tempol (100 μmol/h). Basal MAP and renal vascular resistance (RVR) were elevated in rats induced with indole-3-carbinol compared with noninduced rats ( n = 5) (184 ± 4 vs. 127 ± 3 mmHg, P < 0.01, and 29 ± 2 vs. 21 ± 1 mmHg·ml−1·min·g, P < 0.01, respectively). Hypertensive rats had elevated excretion of urinary 8-isoprostane compared with normotensive rats (41 ± 4 vs. 13 ± 6 pg·min−1·g−1, P < 0.01). There were no differences in renal plasma flow and glomerular filtration rate between groups. Systemic administration of tempol decreased MAP (184 ± 4 to 151 ± 4 mmHg, P < 0.01) and RVR (29 ± 2 to 25 ± 2 mmHg·ml−1·min·g, P < 0.05) in hypertensive but not in normotensive Cyp1a1-Ren2 rats. In addition, tempol administration decreased urinary excretion of 8-isoprostane (41 ± 4 to 25 ± 4 pg·min−1·g−1, P < 0.05). Renal plasma flow and glomerular filtration rate remained unaltered during tempol administration in both groups. The administration of the nitric oxide synthase inhibitor nitro-l-arginine attenuated the decrease in MAP and RVR in response to tempol. These findings indicate that superoxide anion contributes to the elevated RVR and increased arterial blood pressure, by a mechanism that is at least in part nitric oxide dependent, in Cyp1a1-Ren2 rats with malignant hypertension.

Publisher

American Physiological Society

Subject

Physiology

Reference37 articles.

1. Campbell SJ, Carlotti F, Hall PA, Clark AJ, and Wolf CR. Regulation of the CYP1A1 promoter in transgenic mice: an exquisitely sensitive on-off system for cell specific gene regulation. J Cell Sci 109: 2619–2625, 1996.

2. Cervenka L, Mitchell KD, and Navar LG. Renal function in mice: effects of volume expansion and angiotensin II. J Am Soc Nephrol 10: 2631–2636, 1999.

3. Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics

4. Benzo[alpha]pyrene metabolism, activation and carcinogenesis: role and regulation of mixed-function oxidases and related enzymes.

5. Graciano ML, Mouton C, Patterson ME, Mullins JJ, and Mitchell KD. Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with malignant hypertension (Abstract). FASEB J 19: A548, 2005.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3