Abstract P042: Role Of Angiotensin In Determining Blood Flow Remaining Kidney Following Nephrectomy

Abstract

We have previously presented data obtained in anesthetized Sprague Dawley (SD) rats showing acute increases of the renal blood flow (RBF) in the remaining kidney after unilateral nephrectomy (UNx) which were prevented with the AT1 receptor blocker losartan (ARB). We now chronically monitored RBF for 7 days following UNx in unanesthetized SD rats (6 weeks of age) with daily ARB treatment (oral; 10 mg/Kg; n=6) or vehicle (Vhe; Nutella; n=7) administered every 12 hr, from 5 days before UNx and throughout the entire experimental period. Rats were first instrumented with a Transonic flow probe on the left renal artery and a femoral arterial catheter for 24 hr continuous monitoring of RBF and mean arterial pressure (MAP). A week later, rats were anesthetized with isoflurane, and the right kidney was removed (UNx). After rapid recovery (15 min), RBF and MAP were monitored continuously for the next 7 days. In ARB treated rats, MAP fell an average of 115 to 106 mmHg (p<0.05) and RBF increased from 6.2 to 7.4 ml/min (p=0.06). Following Unx, RBF of both the ARB and Vhe group gradually rose (P<0.05) to an average of 10.6 and 9.9 ml/min (p=0.48) in ARB and Vhe treated groups respectively at day 7 while MAP remained unchanged. A similar increase of kidney weight was observed in both groups. Other SD rats (n=7) were instrumented with a femoral arterial and venous catheter for measurements of GFR following UNx. Rats were trained to wear a jacket carrying a miniaturized light emitting diode for real-time transcutanous excitation and detection of the emitted light to determine disappearance curves following i.v. injection of FITC-Sinistrin. Total GFR decreased from 1.8 to 1.2 ml/min/100gbw 2 days after UNx (p<0.05) and remained at that level for 21 days following UNx. We conclude that following UNx the RBF of the remaining kidney increases independent of changes of the renin-angiotensin system and corresponds to kidney hypertrophy. GFR returned to nearly 70% of the 2 kidney filtration rate 2 days following UNx and remained unchanged for the next 21 days.