Abstract
Background and ObjectiveIncreased 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.MethodsMale rats were subjected to 5/6 nephrectomy (SNx 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 + SNx (n = 12), Sham CL + SNx (n = 9), CL+ Sham SNx (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.ResultsBaseline MAP, HR, RBF, and renal vascular conductance (RVC) were comparable among groups. Baseline GFR was significantly depressed in CL + SNx and Sham CL + SNx groups compared to Sham Control and CL + Sham SNx groups. Upon RVP increase, MAP and HR fell in all groups. Increased RVP exacerbated the reduction in RBF in CL + SNx (−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 + SNx (−6.8 ± 1.3 ml/min) and CL + Sham SNx (−5.1 ± 0.4 ml/min) groups. RVP increase virtually eliminated GFR in CL + SNx (−99 ± 1%), Sham CL + SNx (−95 ± 5%), and CL + Sham SNx (−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 + SNx: −0.035 ± 0.011; CL + Sham SNx: −0.050 ± 0.005 ml/min·mmHg−1, p < 0.05) but not Sham CL + SNx (−0.001 ± 0.019 ml/min·mmHg−1) or Control (−0.033 ± mL/min·mmHg−1).ConclusionChronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats.
Highlights
Significant evidence supports pathophysiological interactions between the heart and the kidneys
Six weeks later, anesthetized rats were subjected to an acute experiment whereupon mean arterial pressure (MAP), heart rate (HR), renal venous pressure (RVP), renal blood flow (RBF), and glomerular filtration rate (GFR) were measured at baseline and during elevation of RVP to 20–25 mmHg for 120 min
Chronic combined heart and kidney failure primarily impairs renal hemodynamic stability in response to elevated RVP compared to healthy rats
Summary
Significant evidence supports pathophysiological interactions between the heart and the kidneys. A major challenge in this field is an incomplete understanding of the nature of interactions between the heart and kidneys This led our group to establish and characterize a rodent model of combined heart and kidney dysfunction (Bongartz et al, 2012a,b) which recapitulates key aspects of human cardiorenal syndrome such as decreased ejection fraction and a low glomerular filtration rate (GFR). We demonstrated that an isolated and chronic increase in RVP in otherwise healthy rats initiates both anatomic and physiologic adaptations which serve to return RVP to the normal range (Hamza et al, 2020) These adaptations attenuate the renal functional response to a superimposed increase in RVP; this occurs at the cost of impaired ability to maintain stable blood pressure and reduced baseline renal perfusion (Hamza et al, 2020). 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
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