Menthol-induced cutaneous vasodilation is preserved in essential hypertensive men and women

Daniel H. Craighead, Lacy Marie Alexander

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

BACKGROUND Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer’s (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax). RESULTS At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. CONCLUSIONS Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.

Original languageEnglish (US)
Pages (from-to)1156-1162
Number of pages7
JournalAmerican journal of hypertension
Volume30
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Menthol
Vasodilation
Skin
Nitric Oxide Synthase
Endothelium
Microdialysis
Laser-Doppler Flowmetry
Lidocaine
Vasodilator Agents
Forearm
Arterial Pressure

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

@article{02d5e1220d4d41fb92541f18446b3367,
title = "Menthol-induced cutaneous vasodilation is preserved in essential hypertensive men and women",
abstract = "BACKGROUND Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer’s (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation ({\%}CVCmax). RESULTS At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. CONCLUSIONS Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.",
author = "Craighead, {Daniel H.} and Alexander, {Lacy Marie}",
year = "2017",
month = "12",
day = "1",
doi = "10.1093/ajh/hpx127",
language = "English (US)",
volume = "30",
pages = "1156--1162",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "12",

}

Menthol-induced cutaneous vasodilation is preserved in essential hypertensive men and women. / Craighead, Daniel H.; Alexander, Lacy Marie.

In: American journal of hypertension, Vol. 30, No. 12, 01.12.2017, p. 1156-1162.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Menthol-induced cutaneous vasodilation is preserved in essential hypertensive men and women

AU - Craighead, Daniel H.

AU - Alexander, Lacy Marie

PY - 2017/12/1

Y1 - 2017/12/1

N2 - BACKGROUND Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer’s (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax). RESULTS At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. CONCLUSIONS Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.

AB - BACKGROUND Menthol is a selective transient receptor potential melastatin 8 (TRPM8) channel agonist that induces cutaneous vasodilation in young, normotensive men and women through nitric oxide synthase (NOS)-, endothelium-derived hyperpolarizing factor (EDHF)-, and sensory nerve-mediated mechanisms. Microvascular dysfunction is present in essential hypertension and whether menthol induces vasodilation is men and women with essential hypertension is equivocal. METHODS Four intradermal microdialysis fibers were placed in the forearm of 9 essential hypertensive and 10 age-matched normotensive control subjects. Sites were pretreated with lactated Ringer’s (control), l-NAME (NOS inhibited), TEA (EDHF inhibited), and lidocaine (sensory nerve inhibited). The microdialysis fibers were then perfused with 7 increasing doses of menthol (0.1-500 mM). Red cell flux in response to menthol was measured with laser Doppler flowmetry. Data were normalized to mean arterial pressure and presented as a percentage of site-specific maximum vasodilation (%CVCmax). RESULTS At the control site, menthol caused vasodilation in both the normotensive and hypertensive groups (menthol doses 100, 250, and 500 mM; all P < 0.05 compared to baseline). There were no differences between groups (P = 0.58, main effect). There was no effect of either NOS or sensory nerve inhibition on menthol-induced vasodilation in the normotensive group; however, menthol-induced vasodilation was attenuated with NOS and sensory nerve inhibition in the hypertensive group. EDHF inhibition attenuated menthol-induced vasodilation in both groups. CONCLUSIONS Menthol-induced vasodilation has NO, EDHF, and sensory nerve components. Menthol-induced cutaneous vasodilation is preserved in hypertensive subjects. However, the hypertensive subjects exhibited a loss of redundant vasodilator systems.

UR - http://www.scopus.com/inward/record.url?scp=85042134466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042134466&partnerID=8YFLogxK

U2 - 10.1093/ajh/hpx127

DO - 10.1093/ajh/hpx127

M3 - Article

VL - 30

SP - 1156

EP - 1162

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 12

ER -