Reduction of circulating renin‐angiotensin following unilateral nephrectomy signals kidney hypertrophy via increase in renal blood flow

Abstract

RationaleThe compensatory hypertrophy of a remaining kidney after nephrectomy has long been recognized and the molecular and functional responses to these events have been well characterized. However, the signal that triggers these events is unknown. Recent studies have found that nephrectomy of the right kidney in rats results in a rapid increase of renal blood flow of the remaining kidney within the first 30 minutes and activation of the mTOR pathway with consequent hypertrophy. In the present study, we hypothesized that a reduction of circulating renin would immediately occur with removal of the right kidney which could produce an immediate peripheral vasodilation and increase of renal blood flow within the remaining left kidney.MethodsSprague Dawley rats (male; 7 wk age) were anesthetized, the left kidney was denervated and then the right kidney was removed while monitoring immediate changes of systemic mean arterial blood pressure (MAP), left renal arterial blood flow (RBF), and left urine volume (V). Three groups were studied: 1) No drug treatment (n=5); 2) Pretreated with the AT1 receptor blocker Losartan (n=4); 3) Pretreated with Losartan and Angiotensin II administered to return aortic pressure and RBF to normal before removing the right kidney (n=2).ResultsLeft RBF gradually increased from 3.8 to 4.7 ml/min and became stable 30 minutes following removal of the right kidney. A slight decrease of MAP occurred during that time (~4 mmHg) and urine volume nearly doubled from 2.7 to 5.3 μl/min. Rats treated with Losartan exhibited a reduced baseline level of MAP and increased level of RBF but the changes in MAP and RBF following right nephrectomy were abolished. Rats treated with Losartan with Angiotensin II infused to normalize baseline levels of RBF and MAP, also exhibited no increases of RBF following removal of the right kidney.ConclusionWe conclude that rapid reductions of circulating renin‐angiotensin following right kidney nephrectomy produce increased RBF in the remaining kidney which in turn may trigger the compensatory hypertrophy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.