Related Experiment Video
Updated: Nov 21, 2025
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Angiotensin II type 1a receptor loss ameliorates chronic tubulointerstitial damage after renal ischemia reperfusion
Yoko Fujita1, Daisuke Ichikawa1, Takeshi Sugaya1
1Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan.
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.
Insights
Suppressing angiotensin II type 1a receptor (AT1a) activation protected against chronic kidney damage after renal ischemia reperfusion (IR) in mice. Inactivating the AT1 receptor may prevent acute kidney injury progression to chronic kidney disease.
Area of Science:
- Nephrology
- Cardiovascular Research
- Molecular Medicine
Background:
- Renal ischemia reperfusion (IR) injury can lead to chronic tubulointerstitial damage (TID).
- The angiotensin II type 1a receptor (AT1a) plays a role in kidney injury pathways.
Purpose of the Study:
- To investigate if suppressing AT1a receptor activation ameliorates severe chronic TID after renal IR.
- To evaluate the renoprotective effects of AT1a receptor inactivation in a mouse model.
Main Methods:
- Unilateral renal ischemia was induced in AT1a knockout (AT1a-/-) and wild-type (AT1a+/+) male mice for 45 minutes.
- Renal damage, atrophy, and tubulointerstitial damage were assessed at 70 days postischemia.
- Systolic blood pressure was monitored, and hydralazine was used in some wild-type mice.
Main Results:
- AT1a-/- mice showed significantly less renal atrophy and severe TID compared to wild-type mice 70 days postischemia.
- Acute tubular injury at 3 days postischemia was similar between groups.
- Hydralazine administration did not replicate the renoprotective effects seen in AT1a-/- mice.
Conclusions:
- Inactivation of the AT1 receptor prevents severe chronic tubulointerstitial damage following renal IR.
- This suggests that targeting the AT1 receptor could be a therapeutic strategy to prevent the progression of acute kidney injury to chronic kidney disease.
Related Concept Videos
01:25Antihypertensive Drugs: Direct Renin Inhibitors
01:29Acute Kidney Injury II: Pathophysiology
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:29Heart Failure II: Pathophysiology