A sex-specific, COX-derived/thromboxane-receptor activator causes depolarization and vasoconstriction in male mice mesenteric resistance arteries

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A sex-specific, COX-derived/thromboxane-receptor activator causes depolarization and vasoconstriction in male mice mesenteric resistance arteries. / Chen, Hua; Simonsen, Ulf; Aalkjaer, Christian.

In: Basic & Clinical Pharmacology & Toxicology, Vol. 127, No. 2, 08.2020, p. 152-159.

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@article{9af374e321c04800b4f589a1bf0ca4b1,
title = "A sex-specific, COX-derived/thromboxane-receptor activator causes depolarization and vasoconstriction in male mice mesenteric resistance arteries",
abstract = "We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9- to 12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice. In the presence of the NO synthase inhibitor N ω-nitro-L-arginine methyl ester (L-NAME), acetylcholine-induced dilation of arteries from males increased in the presence of indomethacin and the COX-1-specific inhibitor FR122047. The presence of indomethacin was also associated with a more negative membrane potential in arteries from males. In arteries from db/db mice, no sex differences were seen. In arteries from male but not female wild-type mice, the thromboxane receptor blocker SQ29,548 increased relaxation to acetylcholine. In contrast to arteries from female mice, COX (most likely COX-1)-derived prostanoids and activation of thromboxane receptors counteract acetylcholine vasodilatation probably through increased smooth muscle depolarization in arteries from male mice. In mice with diabetes and pronounced endothelial dysfunction, inhibition of COX did not enhance acetylcholine vasodilatation. ",
keywords = "acetylcholine, endothelium, indomethacin, membrane potential, resistance arteries, THROMBOXANE A(2), AORTA, BLOOD-PRESSURE, RESPONSES, SMOOTH-MUSCLE, TONE, NITRIC-OXIDE, ENDOTHELIUM-DEPENDENT CONTRACTIONS, DYSFUNCTION, GENDER-DIFFERENCES",
author = "Hua Chen and Ulf Simonsen and Christian Aalkjaer",
note = "This article is protected by copyright. All rights reserved.",
year = "2020",
month = aug,
doi = "10.1111/bcpt.13413",
language = "English",
volume = "127",
pages = "152--159",
journal = "Basic & Clinical Pharmacology & Toxicology",
issn = "1742-7843",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "2",

}

RIS

TY - JOUR

T1 - A sex-specific, COX-derived/thromboxane-receptor activator causes depolarization and vasoconstriction in male mice mesenteric resistance arteries

AU - Chen, Hua

AU - Simonsen, Ulf

AU - Aalkjaer, Christian

N1 - This article is protected by copyright. All rights reserved.

PY - 2020/8

Y1 - 2020/8

N2 - We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9- to 12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice. In the presence of the NO synthase inhibitor N ω-nitro-L-arginine methyl ester (L-NAME), acetylcholine-induced dilation of arteries from males increased in the presence of indomethacin and the COX-1-specific inhibitor FR122047. The presence of indomethacin was also associated with a more negative membrane potential in arteries from males. In arteries from db/db mice, no sex differences were seen. In arteries from male but not female wild-type mice, the thromboxane receptor blocker SQ29,548 increased relaxation to acetylcholine. In contrast to arteries from female mice, COX (most likely COX-1)-derived prostanoids and activation of thromboxane receptors counteract acetylcholine vasodilatation probably through increased smooth muscle depolarization in arteries from male mice. In mice with diabetes and pronounced endothelial dysfunction, inhibition of COX did not enhance acetylcholine vasodilatation.

AB - We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9- to 12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice. In the presence of the NO synthase inhibitor N ω-nitro-L-arginine methyl ester (L-NAME), acetylcholine-induced dilation of arteries from males increased in the presence of indomethacin and the COX-1-specific inhibitor FR122047. The presence of indomethacin was also associated with a more negative membrane potential in arteries from males. In arteries from db/db mice, no sex differences were seen. In arteries from male but not female wild-type mice, the thromboxane receptor blocker SQ29,548 increased relaxation to acetylcholine. In contrast to arteries from female mice, COX (most likely COX-1)-derived prostanoids and activation of thromboxane receptors counteract acetylcholine vasodilatation probably through increased smooth muscle depolarization in arteries from male mice. In mice with diabetes and pronounced endothelial dysfunction, inhibition of COX did not enhance acetylcholine vasodilatation.

KW - acetylcholine

KW - endothelium

KW - indomethacin

KW - membrane potential

KW - resistance arteries

KW - THROMBOXANE A(2)

KW - AORTA

KW - BLOOD-PRESSURE

KW - RESPONSES

KW - SMOOTH-MUSCLE

KW - TONE

KW - NITRIC-OXIDE

KW - ENDOTHELIUM-DEPENDENT CONTRACTIONS

KW - DYSFUNCTION

KW - GENDER-DIFFERENCES

UR - http://www.scopus.com/inward/record.url?scp=85085133833&partnerID=8YFLogxK

U2 - 10.1111/bcpt.13413

DO - 10.1111/bcpt.13413

M3 - Journal article

C2 - 32291865

VL - 127

SP - 152

EP - 159

JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7843

IS - 2

ER -