摘要：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.
