{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:23:14Z","timestamp":1771953794536,"version":"3.50.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:p>Substance P is released from nerve endings in the heart under pathological conditions like ischemia, but its action on cardiac cells has not been investigated. This study tested the hypothesis that substance P is mitogenic to adult cardiac fibroblasts and delineated the underlying mechanism(s). Substance P, acting via neurokinin-1 (NK-1) receptors, stimulated cellular hyperplasia over a range of 1\u201310 \u03bcmol\/l. It elicited no change in net collagen production, total protein synthesis, or cell protein content but increased<jats:sup>45<\/jats:sup>Ca uptake and superoxide generation. EGTA, N-acetyl-cysteine, and superoxide dismutase attenuated the hyperplastic response to substance P. A combination of substance P and EGTA enhanced superoxide generation without an increase in DNA synthesis, showing that an increase in superoxide production does not result in hyperplasia when extracellular Ca<jats:sup>2+<\/jats:sup>is chelated. Together, the data suggest that substance P may activate, via NK-1 receptors, a hyperplastic but not hypertrophic response in adult cardiac fibroblasts and that alterations in redox state and Ca<jats:sup>2+<\/jats:sup>homeostasis may act in concert to mediate its mitogenic action.<\/jats:p>","DOI":"10.1152\/ajpheart.00747.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:02:41Z","timestamp":1425412961000},"page":"H1855-H1862","source":"Crossref","is-referenced-by-count":52,"title":["Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts"],"prefix":"10.1152","volume":"282","author":[{"given":"C.","family":"Kumaran","sequence":"first","affiliation":[{"name":"Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India 695 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