Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin.
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 H1 and H2 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 < 0.05). Inhibition of H1 receptors attenuates the rise in CVC to exogenous VIP (P < 0.05); however, combined H1-receptor inhibition and NO synthase inhibition further reduced VIP-mediated vasodilation compared with either H1 inhibition or NO synthase inhibition alone (P < 0.05). In contrast to H1-receptor inhibition, H2-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 H1- and H2-receptor activation.
Wilkins
Brad W
BW
Department of Human Physiology , University of Oregon, Eugene, Oregon 97403, USA.
Chung
Linda H
LH
Tublitz
Nathan J
NJ
Wong
Brett J
BJ
Minson
Christopher T
CT
D000287:Administration, Topical; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods; D009569:Nitric Oxide / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D011968:Receptors, Histamine; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide