Hydrogen peroxide generated by NADPH oxidase 4 contributes to transient receptor potential vanilloid 1 channel-mediated mechanosensation in the rat kidney.

This study tested whether H2O2 derived from Nox4 affects TRPV1 function in renal sensory responses. Perfusion of H2O2 into the renal pelvis dose-dependently increased afferent renal nerve activity (ARNA) and substance P (SP) release. These responses were attenuated by co-treatment with catalase or TRPV1 blockers. In single-unit recordings, H2O2 activated ARNA in response to rising IPP, but not high salt. Western blots revealed that Nox2 (gp91phox) and Nox4 are both present in rat kidney, but Nox4 is abundant in the renal pelvis and originates from dorsal root ganglia. This distribution was associated with the expression of the Nox4 regulators, p22phox and polymerase delta-interacting protein 2 (Poldip2). Co-immunoprecipitation experiments showed that IPP increases Poldip2 association with Nox4 or p22phox in the renal pelvis. Interestingly, immunofluorescence labeling demonstrated that Nox4 co-localizes with TRPV1 in the sensory fibers of the renal pelvis, indicating that H2O2 generated from Nox4 may affect TRPV1 activity. Stepwise increases in IPP and saline loading resulted in H2O2 and SP release, sensory activation, diuresis, and natriuresis. These effects, however, were remarkably attenuated by Nox inhibition. Overall, these results suggest that Nox4-positive fibers liberate H2O2 after mechano-stimulation, thereby contributing to a renal sensory nerve-mediated diuretic/natriuretic response. PMID: 26136558 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research