Abstract P056: MHC CLass II-associated Invariant Peptide (CLIP) Antagonism During Chronic Lipopolysaccharide Treatment Preserves Afferent Arteriolar Autoregulatory Behavior

Lipopolysaccharide (LPS) is a cell wall component of gram-negative bacteria that can activate toll-like receptor 4, which in turn, activates the innate immune system. Chronic immune system activation is linked to blunted afferent arteriolar autoregulatory behavior and kidney injury. MHC Class II-associated invariant peptide (CLIP) provides a critical step in antigen processing, presentation, and adaptive immune system activation. Accordingly, we postulated that treatment with a competitive CLIP antagonist (CAP) during chronic low-dose LPS exposure would preserve afferent arteriolar autoregulatory behavior. Rats were implanted with osmotic minipumps (day 0) for infusion of LPS (0.01mg/kg/day) or saline (0.9% NaCl; 0.5μl/hr) for 8 days and then the kidneys were harvested for juxtamedullary nephron studies. Four groups (n=6/group) were studied: Control, LPS, LPS + CAP and Sham + CAP. Both LPS + CAP and Sham + CAP groups were treated with CAP (3mg/kg/day; i.p.) on days 1-7. Autoregulatory behavior was assessed in these groups by increasing perfusion pressure in 15 mmHg increments from 65 to 170 mmHg. Starting baseline diameters were similar across the control (15.2 ± 1.2 μm), LPS (14.1 ± 1.0 μm), LPS + CAP (15.1 ± 1.0), and Sham + CAP (15.7 ± 0.6) groups. When perfusion pressure was increased from 65 to 170 mmHg, control and sham + CAP afferent arteriolar diameter decreased significantly by 26 ± 4% and 25 ± 2% (P