Angiotensin II type 1a receptor loss ameliorates chronic tubulointerstitial damage after renal ischemia reperfusion

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.

Automated summary

The study showed that inhibiting the activation of the AT1 receptor can improve severe chronic tubulointerstitial damage after renal ischemia reperfusion, but the same renoprotective effects were not reproduced by the antihypertensive drug hydralazine.