{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:26:14Z","timestamp":1785860774992,"version":"3.56.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>Vasoactive intestinal peptide (VIP) is known to induce histamine release in human skin and to include a nitric oxide (NO)-dependent dilation in several other vascular beds. However, the relative contribution of histamine and NO to VIP-mediated vasodilation in human skin is unknown. Forty-three subjects volunteered to participate in two studies designed to examine the mechanism of VIP-mediated vasodilation in human skin. Study 1 examined the contribution of NO in the skin blood flow response to eight doses of VIP ranging from 25 to 800 pmol. In addition, study 1 examined a specific role for NO in VIP-mediated dilation. Study 2 examined the relative contribution of NO and histamine to VIP-mediated dilation via H<jats:sub>1<\/jats:sub>and H<jats:sub>2<\/jats:sub>histamine receptors. Infusions were administered to skin sites via intradermal microdialysis. Red blood cell flux was measured by using laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC; LDF\/mean arterial pressure) was calculated and normalized to maximal vasodilation. VIP-mediated vasodilation includes a NO-dependent component at doses above 100 pmol, where NO synthase inhibition significantly attenuates CVC ( P &lt; 0.05). Inhibition of H<jats:sub>1<\/jats:sub>receptors attenuates the rise in CVC to exogenous VIP ( P &lt; 0.05); however, combined H<jats:sub>1<\/jats:sub>-receptor inhibition and NO synthase inhibition further reduced VIP-mediated vasodilation compared with either H<jats:sub>1<\/jats:sub>inhibition or NO synthase inhibition alone ( P &lt; 0.05). In contrast to H<jats:sub>1<\/jats:sub>-receptor inhibition, H<jats:sub>2<\/jats:sub>-receptor inhibition did not affect vasodilation to exogenous VIP. Thus, in human skin, VIP-mediated vasodilation includes a NO-dependent component that could not be explained by H<jats:sub>1<\/jats:sub>- and H<jats:sub>2<\/jats:sub>-receptor activation.<\/jats:p>","DOI":"10.1152\/japplphysiol.00366.2004","type":"journal-article","created":{"date-parts":[[2004,5,25]],"date-time":"2004-05-25T00:58:25Z","timestamp":1085446705000},"page":"1291-1298","source":"Crossref","is-referenced-by-count":61,"title":["Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin"],"prefix":"10.1152","volume":"97","author":[{"given":"Brad W.","family":"Wilkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda H.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Tublitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett 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