ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO118

Acute and Chronic Renal Ischemia-Reperfusion Injury and Angiotensin II-Induced Hypertension Are Attenuated in Mice with Proximal Tubule-Selective Deletion of Angiotensin AT1a Receptors

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Li, Xiao C., The University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Zhang, Jian Feng, Guangxi Medical University, Nanning, China
  • Zheng, Xiao Wen, Guangxi Medical University, Nanning, China
  • Zhuo, Jia L., The University of Mississippi Medical Center, Jackson, Mississippi, United States
Background

The present study tested the hypothesis that genetic deletion of angiotensin II (ANG II) AT1a receptors selectively in the proximal tubule of the kidney attenuates renal ischemia-reperfusion injury and ANG II-induced hypertension in mice.

Methods

Proximal tubule-specific AT1a receptor-knockout mice (PT-AT1a-KO) were generated using the standard Cre/LoxP recombination approach. Adult male C57BL/6J (WT), global AT1a-KO, and PT-AT1a-KO mice were subjected to sham surgery or 45 min bilateral renal ischemia, followed by reperfusion for 24 h or 7 days. ANG II-dependent hypertension was induced by infusing ANG II at 1.5 mg/kg/day, i.p., for 2 weeks. Systolic blood pressure (SBP), renal function, glomerular, tubuointerstital, and perivascular fibrotic responses were determined and compared

Results

Basal systolic blood pressure was 22 ± 5 mmHg lower in global AT1a-KO or 11 ± 3 mmHg lower in PT-AT1a-KO mice (p<0.05 vs. WT). WT mice developed significant glomerular, cortical tubulointerstitial and perivascular injury 24 h or 7 days after renal ischemia-reperfusion was induced (p<0.01). Ischemia and reperfusion renal injury was not prevented in global AT1a-KO mice (n.s. vs. WT), but it was significantly attenuated in PT-AT1a-KO mice 24 h or 7 days after renal ischemia-reperfusion was induced (p<0.05 vs. WT or AT1a-KO). WT developed severe ANG II-induced hypertension, as expected, but it was significantly attenuated in PT-AT1a-KO mice (p<0.01 vs. WT).

Conclusion

We concluded that AT1a receptors in the proximal tubule of the kidney play a key role in the pathogenesis of renal ischemia-reperfusion injury and ANG II-dependent hypertension.

Funding

  • NIDDK Support