Activation of Transient Receptor Potential Vanilloid Type 1 Channels by N-octanoyl Dopamine Improves Renal Function after Warm Ischemia but Not after Prolonged Cold Preservation.

Abstract

Aim: N-octanoyl dopamine (NOD) improves renal function, when applied shortly before induction of acute kidney injury (AKI). It remains to be assessed how NOD convey its renoprotective properties, if NOD also protects after AKI induction, and if renal allograft recipients also benefit from NOD treatment. Methods: AKI was induced by clamping the left renal artery (45min) in unilateral nephrectomized Lewis or Spaque Dawley (SD), wild type (WT) and TRPV1-/- rats. Transplantations were performed in the Fisher to Lewis model using a standardized cold ischemia time of 20 hrs. Treatment was installed directly after restoration of organ perfusion. Renal function, histology and perfusion were assessed, by serum creatinine, microscopy and magnetic resonance imaging (MRI) using arterial spin labeling (ASL). Results: NOD significantly improved renal function in AKI in WT Lewis and SD rats, but not in TRPV1-/- SD rats. Improved renal function was paralleled by reduced renal inflammation, yet no differences were found in the expression of inflammatory mediators (adhesion molecules and cytokines). Although MRI-ASL showed a significant lower cortical perfusion in ischemic as compared to non-ischemic kidneys, no influence of NOD was observed. Even though prolonged cold storage did not abrogate TRPV1 activation by NOD, treatment of renal allograft recipients did not show a salutary effect. Conclusions: While NOD treatment improves renal function after warm ischemia induced AKI, it does not so after prolonged cold ischemia. Since the renoprotective effect of NOD depends on TRPV1 activation, it remains to be assessed why its salutary effect is lost after prolonged cold ischemia.