{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:23:57Z","timestamp":1789885437771,"version":"4.0.1"},"reference-count":46,"publisher":"American Physiological Society","issue":"4","funder":[{"name":"Chi-Mei Medical Center","award":["CMFJ10107"],"award-info":[{"award-number":["CMFJ10107"]}]},{"DOI":"10.13039\/501100009974","name":"Cardinal Tien Hospital","doi-asserted-by":"crossref","award":["CTH-99-1-2A42"],"award-info":[{"award-number":["CTH-99-1-2A42"]}],"id":[{"id":"10.13039\/501100009974","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009974","name":"Cardinal Tien Hospital","doi-asserted-by":"crossref","award":["7001179"],"award-info":[{"award-number":["7001179"]}],"id":[{"id":"10.13039\/501100009974","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry Science and Technology in Taiwan","award":["NSC98-2314-B-030-004-MY3"],"award-info":[{"award-number":["NSC98-2314-B-030-004-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2015,8,15]]},"abstract":"<jats:p> The presence of NADPH oxidase (Nox) in the kidney, especially Nox4, results in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production, which regulates Na<jats:sup>+<\/jats:sup> excretion and urine formation. Redox-sensitive transient receptor potential vanilloid 1 channels (TRPV1s) are distributed in mechanosensory fibers of the renal pelvis and monitor changes in intrapelvic pressure (IPP) during urine formation. The present study tested whether H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> derived from Nox4 affects TRPV1 function in renal sensory responses. Perfusion of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> into the renal pelvis dose dependently increased afferent renal nerve activity and substance P (SP) release. These responses were attenuated by cotreatment with catalase or TRPV1 blockers. In single unit recordings, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> activated afferent renal nerve activity in response to rising IPP but not high salt. Western blots revealed that Nox2 (gp91<jats:sup> phox<\/jats:sup>) and Nox4 are both present in the rat kidney, but Nox4 is abundant in the renal pelvis and originates from dorsal root ganglia. This distribution was associated with expression of the Nox4 regulators p22<jats:sup> phox<\/jats:sup> and polymerase \u03b4-interacting protein 2. Coimmunoprecipitation experiments showed that IPP increases polymerase \u03b4-interacting protein 2 association with Nox4 or p22<jats:sup> phox<\/jats:sup> in the renal pelvis. Interestingly, immunofluorescence labeling demonstrated that Nox4 colocalizes with TRPV1 in sensory fibers of the renal pelvis, indicating that H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> generated from Nox4 may affect TRPV1 activity. Stepwise increases in IPP and saline loading resulted in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> 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 H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> after mechanostimulation, thereby contributing to a renal sensory nerve-mediated diuretic\/natriuretic response. <\/jats:p>","DOI":"10.1152\/ajprenal.00462.2014","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T02:41:05Z","timestamp":1435804865000},"page":"F369-F376","source":"Crossref","is-referenced-by-count":34,"title":["H<sub>2<\/sub>O<sub>2<\/sub> generated by NADPH oxidase 4 contributes to transient receptor potential vanilloid 1 channel-mediated mechanosensation in the rat kidney"],"prefix":"10.1152","volume":"309","author":[{"given":"Chian-Shiung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Surgery, Liou-Ying Hospital, Chi-Mei Medical Center, Tainan Hsien, 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