慢性心脏和肾脏联合功能障碍加剧肾静脉压力诱导的大鼠肾功能抑制
Chronic, Combined Cardiac and Renal Dysfunction Exacerbates Renal Venous Pressure-Induced Suppression of Renal Function in Rats.
作者信息
Hamza Shereen M, Huang Xiaohua, Zehra Tayyaba, Zhuang Wenqing, Cupples William A, Braam Branko
机构信息
Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Department of Physiology, University of Alberta, Edmonton, AB, Canada.
出版信息
Front Physiol. 2022 Feb 4;13:781504. doi: 10.3389/fphys.2022.781504. eCollection 2022.
BACKGROUND AND OBJECTIVE
Increased renal venous pressure (RVP) is common in combined heart and kidney failure. We previously showed that acute RVP elevation depresses renal blood flow (RBF), glomerular filtration rate (GFR), and induces renal vasoconstriction in the absence of changes in blood pressure in healthy rats. We used our established rodent model of chronic combined heart and kidney failure (H/KF) to test whether RVP elevation would impair cardiovascular stability, renal perfusion and exacerbate renal dysfunction.
METHODS
Male rats were subjected to 5/6 nephrectomy (SN or Sham) and 6% high salt diet followed 7 weeks later by ligation of the left anterior descending coronary artery (CL or Sham). Experimental groups: CL + SN ( = 12), Sham CL + SN ( = 9), CL+ Sham SN ( = 6), and Sham Control ( = 6). Six weeks later, anesthetized rats were subjected to an acute experiment whereupon mean arterial pressure (MAP), heart rate (HR), RVP, RBF, and GFR were measured at baseline and during elevation of RVP to 20-25 mmHg for 120 min.
RESULTS
Baseline MAP, HR, RBF, and renal vascular conductance (RVC) were comparable among groups. Baseline GFR was significantly depressed in CL + SN and Sham CL + SN groups compared to Sham Control and CL + Sham SN groups. Upon RVP increase, MAP and HR fell in all groups. Increased RVP exacerbated the reduction in RBF in CL + SN (-6.4 ± 0.9 ml/min) compared to Sham Control (-3.7 ± 0.9 ml/min, < 0.05) with intermediate responses in Sham CL + SN (-6.8 ± 1.3 ml/min) and CL + Sham SN (-5.1 ± 0.4 ml/min) groups. RVP increase virtually eliminated GFR in CL + SN (-99 ± 1%), Sham CL + SN (-95 ± 5%), and CL + Sham SN (-100%) groups compared to Sham Control (-84 ± 15% from baseline; < 0.05). Renal vascular conductance dropped significantly upon RVP increase in rats with HF (CL + SN: -0.035 ± 0.011; CL + Sham SN: -0.050 ± 0.005 ml/min·mmHg, < 0.05) but not Sham CL + SN (-0.001 ± 0.019 ml/min·mmHg) or Control (-0.033 ± mL/min·mmHg).
CONCLUSION
Chronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats.
背景与目的
肾静脉压力（RVP）升高在合并心力衰竭和肾衰竭时很常见。我们之前发现，在健康大鼠中，急性RVP升高会降低肾血流量（RBF）、肾小球滤过率（GFR），并在血压无变化的情况下诱发肾血管收缩。我们利用已建立的慢性心力衰竭和肾衰竭（H/KF）啮齿动物模型，来测试RVP升高是否会损害心血管稳定性、肾灌注并加重肾功能障碍。
方法
雄性大鼠接受5/6肾切除术（SN或假手术）并给予6%高盐饮食，7周后结扎左冠状动脉前降支（CL或假手术）。实验组：CL + SN（n = 12）、假手术CL + SN（n = 9）、CL + 假手术SN（n = 6）和假手术对照组（n = 6）。六周后，对麻醉的大鼠进行急性实验，在基线以及将RVP升高至20 - 25 mmHg并持续120分钟期间，测量平均动脉压（MAP）、心率（HR）、RVP、RBF和GFR。
结果
各实验组间基线MAP、HR、RBF和肾血管传导率（RVC）相当。与假手术对照组和CL + 假手术SN组相比，CL + SN组和假手术CL + SN组的基线GFR显著降低。RVP升高后，所有组的MAP和HR均下降。与假手术对照组（-3.7 ± 0.9 ml/min，P < 0.05）相比，RVP升高使CL + SN组（-6.4 ± 0.9 ml/min）的RBF降低更为明显，假手术CL + SN组（-6.8 ± 1.3 ml/min）和CL + 假手术SN组（-5.1 ± 0.4 ml/min）的反应介于两者之间。与假手术对照组（较基线降低-84 ± 15%；P < 0.05）相比，RVP升高几乎使CL + SN组（-99 ± 1%）、假手术CL + SN组（-95 ± 5%）和CL + 假手术SN组（-100%）的GFR消失。心力衰竭大鼠RVP升高后肾血管传导率显著下降（CL + SN组：-0.035 ± 0.011；CL + 假手术SN组：-0.050 ± 0.005 ml/min·mmHg，P < 0.05），而假手术CL + SN组（-0.001 ± 0.019 ml/min·mmHg）和对照组（-0.033 ± ml/min·mmHg）则无明显变化。
结论
与健康大鼠相比，慢性心力衰竭和肾衰竭主要损害了肾血流动力学对RVP升高的稳定性。
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