Abstract
We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a−/−) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a−/− and wild-type (AT1a+/+) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a+/+ mice, such a development was not provoked in the AT1a−/− mice. Although the AT1a+/+ mice were administered hydralazine to maintain the same systolic blood pressure (SBP) levels as the AT1a−/− mice with lower SBP levels, hydralazine did not reproduce the renoprotective effects observed in the AT1a−/− mice. Acute tubular injury at 3 days postischemia was similar between the AT1a−/− mice and the AT1a+/+ mice. From our investigations using IR kidneys at 3, 14, and 28 days postischemia, the multiple molecular mechanisms may be related to prevention of severe chronic TID postischemia in the AT1a−/− mice. In conclusion, inactivation of the AT1 receptor may be useful in preventing the transition of acute kidney injury to chronic kidney disease.
Highlights
We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a−/−) male mice
Because the renal ischemic reperfusion (IR) model is generally used to reflect the pathology of ischemic acute kidney injury (AKI) and subsequent chronic kidney disease (CKD) observed in clinical p ractice[16,17,18], we investigated whether suppressed activation of the angiotensin II type 1a (AT1a) receptor could ameliorate severe chronic TID after renal IR using AT1a knockout homozygous ( AT1a−/−) male mice
We found marked renal atrophy and severe chronic TID, which is similar to the renal pathology represented in human end stage renal disease (ESRD), at 70 days postischemia in a renal unilateral IR model of wild-type (AT1a+/+) mice with renal ischemia induced by clamping of the right renal pedicle for 45 min
Summary
We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a−/−) male mice. From our investigations using IR kidneys at 3, 14, and 28 days postischemia, the multiple molecular mechanisms may be related to prevention of severe chronic TID postischemia in the AT1a−/− mice. Because the renal ischemic reperfusion (IR) model is generally used to reflect the pathology of ischemic AKI and subsequent CKD observed in clinical p ractice[16,17,18], we investigated whether suppressed activation of the angiotensin II type 1a (AT1a) receptor could ameliorate severe chronic TID after renal IR using AT1a knockout homozygous ( AT1a−/−) male mice. A T1a−/− male mice were used in the present study
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