Chronic, Combined Cardiac and Renal Dysfunction Exacerbates Renal Venous Pressure-Induced Suppression of Renal Function in Rats

Shereen M Hamza; Xiaohua Huang; Tayyaba Zehra; Wenqing Zhuang; William A Cupples; Branko Braam

doi:10.3389/fphys.2022.781504

Chronic, Combined Cardiac and Renal Dysfunction Exacerbates Renal Venous Pressure-Induced Suppression of Renal Function in Rats

Front Physiol. 2022 Feb 4:13:781504. doi: 10.3389/fphys.2022.781504. eCollection 2022.

Authors

Shereen M Hamza^{1

2}, Xiaohua Huang¹, Tayyaba Zehra¹, Wenqing Zhuang¹, William A Cupples³, Branko Braam^{1

2}

Affiliations

¹ Division of Nephrology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
² Department of Physiology, University of Alberta, Edmonton, AB, Canada.
³ Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.

Abstract

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_x 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_x (n = 12), Sham CL + SN_x (n = 9), CL+ Sham SN_x (n = 6), and Sham Control (n = 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_x and Sham CL + SN_x groups compared to Sham Control and CL + Sham SN_x groups. Upon RVP increase, MAP and HR fell in all groups. Increased RVP exacerbated the reduction in RBF in CL + SN_x (-6.4 ± 0.9 ml/min) compared to Sham Control (-3.7 ± 0.9 ml/min, p < 0.05) with intermediate responses in Sham CL + SN_x (-6.8 ± 1.3 ml/min) and CL + Sham SN_x (-5.1 ± 0.4 ml/min) groups. RVP increase virtually eliminated GFR in CL + SN_x (-99 ± 1%), Sham CL + SN_x (-95 ± 5%), and CL + Sham SN_x (-100%) groups compared to Sham Control (-84 ± 15% from baseline; p < 0.05). Renal vascular conductance dropped significantly upon RVP increase in rats with HF (CL + SN_x: -0.035 ± 0.011; CL + Sham SN_x: -0.050 ± 0.005 ml/min·mmHg^-1, p < 0.05) but not Sham CL + SN_x (-0.001 ± 0.019 ml/min·mmHg^-1) or Control (-0.033 ± mL/min·mmHg^-1).

Conclusion: Chronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats.

Keywords: blood pressure; combined cardiac and renal dysfunction; glomerular filtration rate; renal blood flow; renal venous congestion.