{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:00:12Z","timestamp":1789412412074,"version":"build-2803163510"},"reference-count":36,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Substance P (SP), a neurokinin-1 receptor (NK-1R) agonist, is mainly produced and stored in primary sensory nerves and, upon its release, participates in cardiovascular and renal functional regulation. This study tests the hypothesis that activation of the NK-1Rs by SP occurs during hypertension induced by deoxycorticosterone (DOCA)-salt treatment, which contributes to renal injury in this model. C57BL\/6 mice were subjected to uninephrectomy and DOCA-salt treatment in the presence or absence of administration of selective NK-1 antagonists, L-733,060 (20 mg\/kg\u00b7d, ip) or RP-67580 (8 mg\/kg\u00b7d, ip). Five weeks after the treatment, mean arterial pressure determined by the telemetry system increased in DOCA-salt mice but without difference between NK-1R antagonist-treated or NK-1R antagonist-untreated DOCA-salt groups. Plasma SP levels were increased in DOCA-salt compared with control mice (P &amp;lt; 0.05). Renal hypertrophy and increased urinary 8-isoprostane and albumin excretion were observed in DOCA-salt compared with control mice (P &amp;lt; 0.05). Periodic acid-Schiff and Masson's trichrome staining showed more severe glomerulosclerosis and tubulointerstitial injury in the renal cortex in DOCA-salt compared with control mice, respectively (P &amp;lt; 0.05). Hydroxyproline assay and F4\/80-staining showed that renal collagen levels and interstitial monocyte\/macrophage infiltration were greater in DOCA-salt compared with control mice, respectively (P &amp;lt; 0.05). Blockade of the NK-1R with L-733,060 or RP-67580 in DOCA-salt mice suppressed increments in urinary 8-isoprostane and albumin excretion, interstitial monocyte\/macrophage infiltration, and glomerulosclerosis and tubulointerstitial injury and fibrosis (P &amp;lt; 0.05). Thus, our data show that blockade of the NK-1Rs alleviates renal functional and tissue injury in the absence of alteration in blood pressure in DOCA-salt-hypertensive mice. The results suggest that elevated SP levels during DOCA-salt hypertension play a significant role contributing to renal damage possibly via enhancing oxidative stress and macrophage infiltration of the kidney.<\/jats:p>","DOI":"10.1210\/en.2012-1284","type":"journal-article","created":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T01:59:58Z","timestamp":1349056798000},"page":"5972-5979","source":"Crossref","is-referenced-by-count":15,"title":["Role of Substance P in Renal Injury During DOCA-Salt Hypertension"],"prefix":"10.1210","volume":"153","author":[{"given":"Youping","family":"Wang","sequence":"first","affiliation":[{"name":"Central Laboratory and Division of Cardiology (Y.W.), First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna H.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine (D.H.W.), Neuroscience Program, and Cell and 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