Abstract 301: Testosterone propionate in Ischemia-reperfusion (I/R) induced Acute Kidney Injury (AKI)
Acute kidney injury (AKI) is a leading cause of morbidity and mortality, and men are more prone to AKI than women implicating androgens as a causative factor whereas estrogens have been thought to be protective. These effects are independent of both androgen and estrogen receptors. We showed recently that infusion of testosterone 3 hrs post reperfusion protected rats from renal injury following ischemia/reperfusion (I/R). In the present study, we tested the hypothesis that testosterone works as a renal vasodilator perhaps by increasing nitric oxide. Male SD rats (8-14 wks; n=3-5/grp) were subjected to sham surgery or I/R induced AKI with bilateral clamping of renal vessels for 30 min. Three hrs after reperfusion, rats were given testosterone propionate (20 μg/kg iv over 10 min) or vehicle (0.75%EtOH). Rats were placed in metabolism cages for 24hrs for nitrate/nitrite excretion (UNOxV), and euthanized and blood taken for creatinine (PCr). I/R increased PCr and decreased UNOxV, compared to shams (0.58±0.05 vs. 3.99±0.36 mg/dL, p<0.0001; UNOxV: 8.54±1.7 vs 1.7±0.78 μmol/day/kg BW, p<0.001). Testosterone attenuated the increase in PCr (2.03±0.23 mg/dL, p< 0.01) but had no effect on UNOxV (3.79±0.91 μmol/day/kg). Pretreatment of rats with L-NAME (1mg/kg/day; dose that did not increase BP) for 48 hours prior to I/R abolished the improvement in PCr with testosterone (PCr: 3.73±0.82 mg/dL, p<0.05 vs no LNAME). Infusion of renal vasodilator PGE2 (30μg/kg iv over 10 min 3 hrs after reperfusion) attenuated PCr compared to I/R alone (2.95±0.21mg/dL, p<0.01) but was independent of increased NO (2.61±0.63 μmol/day/kg, p=NS vs I/R alone), and was not as effective in reducing PCr as testosterone (p<0.05). These data show that low dose testosterone infusion 3 hrs post reperfusion improves renal function in AKI perhaps by causing renal vasodilation. When NO synthesis is blocked, testosterone is incapable of improving PCr after I/R. Furthermore, although the known renal vasodilator PGE2 also improves PCr in I/R, although not as effectively as testosterone. These data continue to support the notion that testosterone infusion has therapeutic potential for the treatment of I/R induced AKI in humans. Supported by NIH R01HL66072, P01HL05971 and AHA 14POST18640015.
Author Disclosures: C.N. Patil: None. R.O. Maranon: None. C. Dalmasso: None. H. Zhang: None. L.A. Juncos: None. J.F. Reckelhoff: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2014 by American Heart Association, Inc.