TRPV1 Channels are involved in niacin-induced cutaneous vasodilation in mice

Clifton, Heather L., Inceoglu, Bora, Ma, Linlin, Zheng, Jie and Schaefer, Saul (2015) TRPV1 Channels are involved in niacin-induced cutaneous vasodilation in mice. Journal of Cardiovascular Pharmacology, 65 2: 184-191. doi:10.1097/FJC.0000000000000181

Author Clifton, Heather L.
Inceoglu, Bora
Ma, Linlin
Zheng, Jie
Schaefer, Saul
Title TRPV1 Channels are involved in niacin-induced cutaneous vasodilation in mice
Journal name Journal of Cardiovascular Pharmacology   Check publisher's open access policy
ISSN 0160-2446
Publication date 2015-02-01
Sub-type Article (original research)
DOI 10.1097/FJC.0000000000000181
Open Access Status Not Open Access
Volume 65
Issue 2
Start page 184
End page 191
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract Niacin is effective in treating dyslipidemias but causes cutaneous vasodilation or flushing, a side effect that limits its clinical use. Blocking prostaglandins in humans reduces but does not consistently eliminate flushing, indicating additional mechanisms may contribute to flushing. The transient receptor potential vanilloid 1 (TRPV1) channel, when activated, causes cutaneous vasodilation and undergoes tachyphylaxis similar to that seen with niacin. Using a murine model, early phase niacin-induced flushing was examined and TRPV1 channel involvement demonstrated using pharmacologic blockade, desensitization, and genetic knockouts (TRPV1 KO). The TRPV1 antagonist AMG9810 reduced the magnitude of the initial and secondary peaks and the rapidity of the vasodilatory response (slope). TRPV1 desensitization by chronic capsaicin reduced the initial peak and slope. TRPV1 KO mice had a lower initial peak, secondary peak, and slope compared with wild-type mice. Chronic niacin reduced the initial peak, secondary peak, and slope in wild-type mice but had no effect in knockout mice. Furthermore, chronic niacin diminished the response to capsaicin in wild-type mice. Overall, these data demonstrate an important role for TRPV1 channels in niacin-induced flushing, both in the acute response and with chronic administration. That niacin-induced flushing is a complex cascade of events, which should inform pharmacological intervention against this side effect.
Keyword Cutaneous vasodilation
TRPV1 channels
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Chemistry and Molecular Biosciences
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Created: Thu, 05 May 2016, 07:01:01 EST by Linlin Ma on behalf of School of Chemistry & Molecular Biosciences