Abstract
mTOR has anti‐inflammatory effect and inhibition of mTOR initiates IL‐12 and IL‐6 production leading to inflammatory response. However; it is not fully known whether mTOR attenuates the inflammation in renal ischemia ‐reperfusion (I/R). We hypothesized that activation of mTOR suppresses the inflammatory response induced by I/R in the kidney. In rats subjected to I/R injury (25 min renal artery occlusion) in the presence or absence of rapamycin, mTOR inhibitor, or Clenbuterol, mTOR activator, markers of renal function, injury and inflammation were measured. In euvolemic anesthetized rats, Rapamycin increased blood pressure (142 ± 5 vs. 120 ± 3mmHg; p<0.05), decreased glomerular filtration rate (2 ± 0.3 to 0.6 ± 0.4 ml/min; p<0.05) and increased urinary sodium excretion (15 ± 2 vs. 107 ± 42 mM/hr; P<0.05).In IR rats (vehicle‐treated), serum creatinine tended to increase (0.5+0.17 vs.1.3+0.1; p>0.05). Rapamycin increased serum creatinine (1.3 ± 0.1 vs. 5 ± 1.6 mg/dl; p<0.05) with no significant difference in serum IL‐6. Clenbuterol tended to antagonize the effect of rapamycin on serum creatinine (3.2 ± 1.6 vs. 5 ± 1.6 mg/dl; p>0.05). In conclusion, mTOR does not appear to play a role in the inflammatory response in renal I/R. However, mTOR plays a role in renal injury via an IL‐6 independent pathway.