Effects of Venous Congestion and Intrarenal Renin‐Angiotensin System Activation on Renal Hemodynamics in Rats with High‐Output Heart Failure

Abstract

Patients suffering from heart failure have a poorer outcome if kidney dysfunction develops. To improve deteriorated renal functions, we first need to fully understand mechanisms that lead to their worsening. Therefore, we set up to investigate which factors contribute to changes in renal hemodynamics observed in heart failure and if manipulation with the renin‐angiotensin system can reverse these changes.Renal hemodynamics were studied under general anesthesia in male Hannover Sprague‐Dawley rats 20 weeks after the creation of an aorto‐caval fistula (ACF). At this stage, heart failure due to placement of an ACF is fully developed (rats suffer from bilateral cardiac hypertrophy, lung congestion) and animals begin to decompensate. Untreated rats with ACF showed significantly decreased mean arterial pressure when compared to sham‐operated rats and treatment with angiotensin‐converting enzyme inhibitor (ACEi) trandolapril (6 mg/l in drinking water) or angiotensin type 1 receptor blocker (ARB) losartan (200 mg/l in drinking water) for 15 weeks further decreased the pressure. We observed a threefold rise in renal vein pressure in rats with ACF, on the other hand, rats on both therapeutic protocols had renal vein pressure similar to that of the control group. Untreated heart failing rats had a substantial decline in renal blood flow (4.98 ± 0.64 ml/min/g) compared to controls (8.87 ± 0.45 ml/min/g), ACE inhibition failed to improve renal perfusion (5.62 ± 0.37 ml/min/g), however treatment with ARB was able to raise renal blood flow to similar values as in control rats (8.89 ± 0.91 ml/min/g). Rats with induced heart failure had a mild but significant reduction of glomerular filtration rate (0.72 ± 0.08 ml/min/g) as compared to sham‐operated rats (1.01 ± 0.03 ml/min/g) and ACE inhibitors as well as ARB preserved glomerular filtration (0.98 ± 0.05 ml/min/g and 0.97 ± 0.03 ml/min/g, respectively).In summary, these findings indicate that angiotensin receptor blockers are effective in preventing renal hypoperfusion in rats with ACF. Failure of ACE inhibitors in raising renal blood flow can be attributed to intrarenal renin‐angiotensin system activation, which circumvents the classic formation of angiotensin II by the angiotensin‐converting enzyme. Nonetheless, glomerular filtration rate remains stable in hypoperfused kidneys, unless there is another factor opposing filtration. We suggest that in untreated rats with ACF this factor is the rise in renal vein pressure, causing congestion in kidneys. We conclude that both renal vein congestion and renal hypoperfusion play important roles in changes in renal hemodynamics in rats with high‐output heart failure and that blockage of the AT1 receptor effectively reverse these changes.Support or Funding InformationThe study was supported by the Charles University, project GA UK No 64217 and by Ministry of Health, Czech Republic ‐ conceptual development of research organization („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001”).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.