Abstract: SA-PO1170
Renal Microvascular Autoregulation in an Ischemia-Reperfusion-Induced Model of Acute Kidney Injury
Session Information
- NIDDK KUH Summer Undergraduate Research Program Posters
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
Group or Team Name
- Bailey McEachen. The University of Alabama at Birmingham, Birmingham, AL.
Background
Autoregulation alters renal vascular resistance (RVR) to keep glomerular filtration rate (GFR) stable during arterial pressure fluctuations. Ischemia-reperfusion-(IR)-induced acute kidney injury exhibits increased RVR and decreased GFR. Our previous study revealed that autoregulation was impaired in IR, but improved with acute treatment of ROS-scavenger and NADPH-oxidase-inhibitor. Therefore, we hypothesize that chronic antioxidant treatment (Tempol) preserves autoregulation by reducing oxidative stress and inflammation in IR rats.
Methods
Rats underwent 60 minute bilateral renal arterial occlusion, with or without Tempol (2mM, drinking water; 7 days), or sham surgery. Afferent arteriole (AA) autoregulatory behavior was assessed in blood-perfused juxtamedullary nephrons. Glomerular function was assessed by plasma creatinine, GFR using FITC-sinistrin, and proteinuria/albuminuria.
Results
SBP was normal across groups: 126-145mmHg (P>0.05) over 7 days. Plasma creatinine increased with IR (1.68±0.18 vs. 0.98±0.04mg/dL in shams, P<0.05), but remained normal in IR+Tempol rats (1.05±0.12mg/dL). Sham rats (n=3) exhibited pressure-dependent vasoconstriction. Control AA diameter averaged 12.2±0.9μm and decreased 32±3% from 65 to 170mmHg. In contrast, IR rats (n=2) lost autoregulatory capacity. AA diameter passively increased by 25% over 65-170mmHg, whereas IR+Tempol rats (n=2) maintained pressure-dependent vasoconstriction. GFR for shams remained constant (0.9-1.3mL/min/100g), while Tempol improved GFR to 0.5 compared to 0.0mL/min/100g in IR. Tempol treatment significantly reduced albuminuria (Day 3: Sham 0.5±0.1mg, IR 14.3±6.6mg, IR+Tempol 2.5±0.5mg) and proteinuria (Day 3: 12±1mg, 58±10mg, and 28±7mg respectively). mRNA expression of inflammatory markers MCP-1/TGF-β increased significantly in IR rats (6.7±1.5/4.0±0.5 vs. 1.1±0.2/1.0±0.1 in sham) and reduced in IR+Tempol rats (3.5±0.4/2.4±0.3).
Conclusion
Ultimately, antioxidant treatment preserved autoregulatory and kidney function in IR rats.