Abstract: TH-PO299

Chronic Tempol Treatment Preserves Afferent Arteriole Autoregulatory Behavior in Renal Ischemia-Reperfusion Rats

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Guan, Zhengrong, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Feng, Wenguang, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Obi, Ijeoma E, University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Pollock, Jennifer S., University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Sanders, Paul W., University of Alabama at Birmingham , Birmingham, Alabama, United States
  • Inscho, Edward W., University of Alabama at Birmingham , Birmingham, Alabama, United States
Background

Inflammation and increased reactive oxygen species (ROS) contribute to impaired renal autoregulatory capability under pathological conditions. We showed that renal ischemia-reperfusion (IR) impairs renal autoregulation in rats 24 hours after IR, but it was restored by acute exposure to the ROS scavenger, tempol. We postulated that chronic tempol treatment would reduce renal inflammation and preserve autoregulation in IR rats.

Methods

Renal IR was induced by bilateral renal artery occlusion (60 min). Renal cortical mRNA expression was measured for NADPH oxidase subunits, cytokines and adhesion molecules. Autoregulation was assessed with the in vitro blood-perfused juxtamedullary nephron preparation on day 7 post IR.

Results

Renal IR significantly increased mRNA expression for p47phox, p67phox, Gp91phox, MCP-1, TGF-β, TNF-α, P-selectin, VCAM and ICAM vs. sham kidneys (n=6/each group). Tempol pre-treatment (2 mM in drinking water) suppressed the IR-induced increase in mRNA expression for all parameters except TGF-β and TNF-α. IR also impaired afferent arteriole autoregulatory behavior. Baseline arteriole diameters were similar in sham, IR and tempol-treated IR kidneys at a renal perfusion pressure (RPP) of 100 mmHg and averaged 13.4±0.3, 11.7±0.8 and 13.4±1.2 µm (n=4-5/each), respectively. Decreasing RPP from 100 to 65 mmHg increased diameter in sham rats by 18±6%. Subsequent increases in RPP (15 mmHg) caused pressure-dependent vasoconstriction and reduced diameter by 30±5% at 170mmHg. In contrast, pressure-mediated diameter changes were blunted in IR rats. Diameter increased by 5±2% and decreased by just 8±9% at 65 and 170 mmHg, respectively (P<0.05 vs. sham), indicating impaired autoregulation. In different IR rats, chronic tempol treatment improved autoregulatory capability. Arteriole diameter increased by 12±1% and decreased by 33±6% at RPP of 65 and 170 mmHg, respectively (P>0.05 vs sham).

Conclusion

In conclusion, these results demonstrate that IR causes renal inflammation and impaired afferent arteriole autoregulatory capability. Scavenging ROS accumulation with tempol preserves normal autoregulatory reactivity, indicating that excessive ROS accumulation contributes importantly to impaired renal autoregulation in IR rats.

Funding

  • NIDDK Support