Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries

Olga Kudryavtseva; Kristina S. Lyngsø; Boye L. Jensen; Henrik Dimke

doi:10.1111/apha.14096

Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries

Olga Kudryavtseva, Kristina S. Lyngsø, Boye L. Jensen, Henrik Dimke^*

^*Corresponding author for this work

University of Southern Denmark

Research output: Contribution to journal › Journal article › Research › peer-review

20 Downloads (Pure)

Abstract

Aim: Magnesium (Mg²⁺) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca²⁺ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg²⁺-dependent vessel relaxation. Methods: To uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg²⁺ were studied in intact and endothelium-denuded aortas. Key findings were confirmed in second-order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg²⁺ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine. Results: Mg²⁺ caused a significant concentration-dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium-denuded aortas. The endothelium-dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg²⁺ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg²⁺ augmented acetylcholine-induced relaxation. SK_Ca and IK_Ca channel blockers apamin and TRAM34 inhibited Mg²⁺-dependent relaxation. The endothelium-independent relaxation in aorta rings was inhibited by high extracellular Ca²⁺. Combined blockade of NO, SK_Ca, and IK_Ca channels significantly reduced Mg²⁺-dependent dilatation in mesenteric resistance vessels. Conclusions: In mouse conductance and resistance arteries Mg²⁺-induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca²⁺ in smooth muscle cells, and additional unidentified mechanisms.

Original language	English
Article number	e14096
Journal	Acta Physiologica
Volume	240
Issue number	3
ISSN	1748-1708
DOIs	https://doi.org/10.1111/apha.14096
Publication status	Published - Mar 2024

Keywords

endothelial function
TRPM7
vascular relaxation
Cricetinae
Cricetulus
Nitric Oxide/metabolism
Vasodilation
Muscle, Smooth, Vascular/metabolism
Animals
Endothelial Cells/metabolism
Magnesium/pharmacology
Mesenteric Arteries
Mice
Biological Factors/metabolism
Endothelium, Vascular
CHO Cells

Documents & Links

10.1111/apha.14096Licence: CC BY-NC-ND

Open Access VersionFinal published version, 11.3 MBLicence: CC BY-NC-ND

Cite this

@article{bc644586262948128a7ed0ee31c3642f,

title = "Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries",

abstract = "Aim: Magnesium (Mg2+) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca2+ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg2+-dependent vessel relaxation. Methods: To uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg2+ were studied in intact and endothelium-denuded aortas. Key findings were confirmed in second-order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg2+ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine. Results: Mg2+ caused a significant concentration-dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium-denuded aortas. The endothelium-dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg2+ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg2+ augmented acetylcholine-induced relaxation. SKCa and IKCa channel blockers apamin and TRAM34 inhibited Mg2+-dependent relaxation. The endothelium-independent relaxation in aorta rings was inhibited by high extracellular Ca2+. Combined blockade of NO, SKCa, and IKCa channels significantly reduced Mg2+-dependent dilatation in mesenteric resistance vessels. Conclusions: In mouse conductance and resistance arteries Mg2+-induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca2+ in smooth muscle cells, and additional unidentified mechanisms.",

keywords = "endothelial function, TRPM7, vascular relaxation, Cricetinae, Cricetulus, Nitric Oxide/metabolism, Vasodilation, Muscle, Smooth, Vascular/metabolism, Animals, Endothelial Cells/metabolism, Magnesium/pharmacology, Mesenteric Arteries, Mice, Biological Factors/metabolism, Endothelium, Vascular, CHO Cells",

author = "Olga Kudryavtseva and Lyngs{\o}, {Kristina S.} and Jensen, {Boye L.} and Henrik Dimke",

year = "2024",

month = mar,

doi = "10.1111/apha.14096",

language = "English",

volume = "240",

journal = "Acta Physiologica",

issn = "1748-1708",

publisher = "Wiley",

number = "3",

}

Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries. / Kudryavtseva, Olga; Lyngsø, Kristina S.; Jensen, Boye L. et al.
In: Acta Physiologica, Vol. 240, No. 3, e14096, 03.2024.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries

AU - Kudryavtseva, Olga

AU - Lyngsø, Kristina S.

AU - Jensen, Boye L.

AU - Dimke, Henrik

PY - 2024/3

Y1 - 2024/3

N2 - Aim: Magnesium (Mg2+) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca2+ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg2+-dependent vessel relaxation. Methods: To uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg2+ were studied in intact and endothelium-denuded aortas. Key findings were confirmed in second-order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg2+ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine. Results: Mg2+ caused a significant concentration-dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium-denuded aortas. The endothelium-dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg2+ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg2+ augmented acetylcholine-induced relaxation. SKCa and IKCa channel blockers apamin and TRAM34 inhibited Mg2+-dependent relaxation. The endothelium-independent relaxation in aorta rings was inhibited by high extracellular Ca2+. Combined blockade of NO, SKCa, and IKCa channels significantly reduced Mg2+-dependent dilatation in mesenteric resistance vessels. Conclusions: In mouse conductance and resistance arteries Mg2+-induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca2+ in smooth muscle cells, and additional unidentified mechanisms.

AB - Aim: Magnesium (Mg2+) is a vasorelaxant. The underlying physiological mechanisms driving this vasorelaxation remain unclear. Studies were designed to test the hypothesis that multiple signaling pathways including nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in endothelial cells as well as Ca2+ antagonization and TRPM7 channels in vascular smooth muscle cells mediate Mg2+-dependent vessel relaxation. Methods: To uncover these mechanisms, force development was measured ex vivo in aorta rings from mice using isometric wire myography. Concentration responses to Mg2+ were studied in intact and endothelium-denuded aortas. Key findings were confirmed in second-order mesenteric resistance arteries perfused ex vivo using pressure myography. Effects of Mg2+ on NO formation were measured in Chinese Hamster Ovary (CHO) cells, isolated mesenteric vessels, and mouse urine. Results: Mg2+ caused a significant concentration-dependent relaxation of aorta rings. This relaxation was attenuated significantly in endothelium-denuded aortas. The endothelium-dependent portion was inhibited by NO and cGMP blockade but not by cyclooxygenase inhibition. Mg2+ stimulated local NO formation in CHO cells and isolated mesenteric vessels without changing urinary NOx levels. High extracellular Mg2+ augmented acetylcholine-induced relaxation. SKCa and IKCa channel blockers apamin and TRAM34 inhibited Mg2+-dependent relaxation. The endothelium-independent relaxation in aorta rings was inhibited by high extracellular Ca2+. Combined blockade of NO, SKCa, and IKCa channels significantly reduced Mg2+-dependent dilatation in mesenteric resistance vessels. Conclusions: In mouse conductance and resistance arteries Mg2+-induced relaxation is contributed by endothelial NO formation, EDHF pathways, antagonism of Ca2+ in smooth muscle cells, and additional unidentified mechanisms.

KW - endothelial function

KW - TRPM7

KW - vascular relaxation

KW - Cricetinae

KW - Cricetulus

KW - Nitric Oxide/metabolism

KW - Vasodilation

KW - Muscle, Smooth, Vascular/metabolism

KW - Animals

KW - Endothelial Cells/metabolism

KW - Magnesium/pharmacology

KW - Mesenteric Arteries

KW - Mice

KW - Biological Factors/metabolism

KW - Endothelium, Vascular

KW - CHO Cells

U2 - 10.1111/apha.14096

DO - 10.1111/apha.14096

M3 - Journal article

C2 - 38258597

AN - SCOPUS:85182820536

SN - 1748-1708

VL - 240

JO - Acta Physiologica

JF - Acta Physiologica

IS - 3

M1 - e14096

ER -

Nitric oxide, endothelium-derived hyperpolarizing factor, and smooth muscle-dependent mechanisms contribute to magnesium-dependent vascular relaxation in mouse arteries

Abstract

Keywords

Documents & Links

Fingerprint

Cite this