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用含血管紧张素 II 和肿瘤坏死因子-α 的高脂/促氧化西方饮食处理的怀孕大鼠对血压升高和肾脏氧化应激具有抗性。

Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-α are resistant to elevations in blood pressure and renal oxidative stress.

作者信息

Cunningham Mark W, West Crystal A, Wen Xuerong, Deng Aihua, Baylis Chris

机构信息

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi;

Department of Physiology and Functional Genomics, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida; and.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2015 Jun 1;308(11):R945-56. doi: 10.1152/ajpregu.00141.2014. Epub 2015 Mar 25.

Abstract

Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-α. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ng·kg(-1)·min(-1)) + TNF-α (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) (n = 7), Virgin + HFD +ANG II and TNF-α (V+HFD) (n = 7), Pregnant + ND + Saline (P+ND) (n = 6), and Pregnant + HFD + ANG II and TNF-α (P+HFD) (n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10-15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOSβ abundance, but no change in kidney cortex NOx content vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-α.

摘要

氧化应激和炎症是妊娠期高血压的危险因素。在此,我们通过遥测技术检测了高脂/促氧化剂西式饮食(HFD)、血管紧张素II(ANG II)和肿瘤坏死因子-α(TNF-α)处理的未孕和妊娠大鼠肾皮质、髓质和主动脉中的24小时平均动脉压(MAP)、一氧化氮(NO)和氧化还原系统。雌性Sprague-Dawley大鼠在交配前8周给予正常饮食(ND)或HFD。妊娠第6天和年龄匹配的未孕大鼠植入微量泵,输注生理盐水或ANG II(150 ng·kg-1·min-1)+TNF-α(75 ng/天),持续14天。分组包括未孕+ND+生理盐水(V+ND)(n = 7)、未孕+HFD+ANG II和TNF-α(V+HFD)(n = 7)、妊娠+ND+生理盐水(P+ND)(n = 6)以及妊娠+HFD+ANG II和TNF-α(P+HFD)(n = 8)。在植入微量泵第6天后,与V+ND大鼠相比,V+HFD大鼠在第7、8和10 - 15天MAP升高。在植入微量泵第6天后,与P+ND大鼠相比,P+HFD大鼠仅在第7天MAP升高。P+HFD大鼠在妊娠晚期24小时MAP、血细胞比容、血浆蛋白浓度和渗透压正常下降。P+HFD大鼠肾皮质、髓质或主动脉氧化应激无变化。与P+ND大鼠相比,P+HFD大鼠nNOSβ丰度降低,但肾皮质NOx含量无变化。接受慢性HFD以及促氧化剂和促炎刺激的妊娠大鼠24小时MAP和肾氧化应激的升高减弱。我们的数据表明,用HFD、ANG II和TNF-α处理的妊娠大鼠肾NO生物利用度未改变。

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