Divergent roles of angiotensin II upon the immediate and sustained increases of renal blood flow following unilateral nephrectomy. Am J Physiol Renal Physiol 2022 May 01;322(5):F473-F485
Date
03/01/2022Pubmed ID
35224992Pubmed Central ID
PMC8977133DOI
10.1152/ajprenal.00376.2021Scopus ID
2-s2.0-85128161119 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Although the molecular and functional responses related to renal compensatory hypertrophy after unilateral nephrectomy (UNX) has been well described, many aspects of these events remain unclear. One question is how the remaining kidney senses the absence of the contralateral organ, and another is what the role of the renin-angiotensin system is in these responses. Both acute anesthetized and chronic unanesthetized experiments were performed using the angiotensin II type 1 receptor blocker losartan and the renin inhibitor aliskiren to determine the contribution of the renin-angiotensin system to immediate changes and losartan for chronic changes of renal blood flow (RBF) and the associated hypertrophic events in male Sprague-Dawley rats. Chronic experiments used implanted RBF probes and arterial catheters for continuous data collection, and the glomerular filtration rate was determined by noninvasive transcutaneous FITC-sinistrin measurements. The results of the acute experiments found that RBF increased nearly 25% (4.6 ± 0.5 to 5.6 ± 0.6 mL/min/g kidney wt) during the first 15 min following UNX and that this response was abolished by losartan (6.7 ± 0.7 to 7.0 ± 0.7 mL/min/g kidney wt) or aliskiren (5.8 ± 0.4 to 6.0 ± 0.4 mL/min/g kidney wt) treatment. Thereafter, RBF increased progressively over 7 days, and kidney weight increased by 19% of pre-UNX values. When normalized to kidney weight determined at day 7 after UNX, RBF was not significantly different from pre-UNX levels. Semiquantification of CD31-positive capillaries revealed increases of the glomeruli and peritubular capillaries that paralleled the kidney hypertrophy. None of these chronic changes was inhibited by losartan treatment, indicating that neither the compensatory structural nor the RBF changes were angiotensin II type 1 receptor dependent.NEW & NOTEWORTHY This study found that the immediate increases of renal blood flow (RBF) following unilateral nephrectomy (UNX) are a consequence of reduced angiotensin II type 1 (AT1) receptor stimulation. The continuous monitoring of RBF and intermittent measurement of glomerular filtration rate (GFR) in conscious rats during the 1-wk period of rapid hypertrophy following UNX provided unique insights into the regulation of RBF and GFR when faced with increased metabolic loads. It was found that neither kidney hypertrophy nor the associated increase of capillaries was an AT1-dependent phenomenon.
Author List
Shimada S, Yang C, Kurth T, Cowley AW JrAuthors
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinSatoshi Shimada Postdoctoral Fellow in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Angiotensin IIAnimals
Kidney
Losartan
Male
Nephrectomy
Rats
Rats, Sprague-Dawley
Renal Circulation
Renin-Angiotensin System
