Data from: Sex-specific vascular effects of menthol: TRPM8 and TRPA1-dependent relaxation in female mouse aorta and pudendal arteries
Data files
Dec 19, 2025 version files 11.97 MB
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Figure_1.pzf
1.07 MB
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Figure_2.pzf
2.66 MB
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Figure_3.pzf
3.19 MB
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Figure_4.pzf
2.07 MB
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Figure_5.pzf
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Figure_6.pzf
1.69 MB
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Figure_Supplemental.pzfx
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README.md
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Abstract
Sexual dysfunction affects the quality of life for both men and women. Menthol, a TRPM8 agonist, is widely used in products to enhance sexual performance due to its cooling effect. Beyond this, menthol also induces vascular effects in male arteries. To explore its effects on female vasculature, we studied male and female C57BL/6 mice, along with female TRPM8 knockout (KO) mice. We isolated the internal pudendal artery and aorta to assess isometric contractile force. Menthol-induced relaxation of the pudendal artery was reduced in both female TRPM8 KO and male mice compared to female controls. Acetylcholine-induced relaxation was not affected in females, but in males, it was attenuated by menthol and enhanced by M8-B, a TRPM8 inhibitor. Menthol did not alter responses to norepinephrine, serotonin, or histamine in either sex. Notably, menthol-induced relaxation was also reduced in the aortas of female TRPM8 KO mice. In both the aorta and pudendal arteries of female mice, the TRPA1 inhibitor HC030031 significantly diminished menthol-induced relaxation. These findings suggest that TRPM8 modulation plays a role in acetylcholine-induced relaxation in male, but not female, pudendal arteries. Moreover, the menthol vascular effect in female arteries relies on TRPM8 and TRPA1 activation.
Dataset DOI: 10.5061/dryad.t1g1jwtgv
Description of the data and file structure
Pudendal and aortic artery rings (2 mm) were mounted on wire or pin myographs and maintained in oxygenated Krebs–bicarbonate solution at 37 °C; pudendal arteries were normalized using dedicated software, whereas aortic rings were set to a passive tension of 5 mN. For vascular reactivity studies, arterial rings were precontracted with phenylephrine, except during norepinephrine and serotonin concentration–response experiments, and cumulative concentration–response curves were constructed for norepinephrine, serotonin, acetylcholine, histamine, or menthol in the absence or following incubation with menthol, M8-B, or HC030031.
All data are presented as mean ± standard error of the mean (SEM), where n denotes the number of independent mice. Concentration–response curves with a clear sigmoidal profile were analyzed by nonlinear regression, whereas curves that did not reach a maximal response or lacked a sigmoidal shape (menthol and histamine) are shown as connected data points to illustrate trends without extrapolation. Comparisons between experimental groups were performed using unpaired Student’s t test or two-way analysis of variance (ANOVA) followed by Šídák’s multiple-comparisons test, as appropriate, with P < 0.05 considered statistically significant. For two-way ANOVA analyses, differences between concentration–response curves were assessed based on the significance of the column (group) factor, as indicated by the F value. All statistical analyses were conducted using GraphPad Prism software (version 9.5.0; GraphPad Software Inc., La Jolla, CA, USA).
Files and variables
File: Figure_1.pzf
Description: Percentage of relaxation to cumulative concentrations of menthol in pudendal arteries precontracted with phenylephrine (1microMolar). A: comparison of female vs male. B: comparison of female control vs female TRPM8 KO mice.
File: Figure_2.pzf
Description: Percentage of relaxation to cumulative concentrations of acetylcholine in pudendal arteries precontracted with phenylephrine (1microMolar). A: comparison of response in female mice in control vs under menthol (30 microMolar) incubation. B: comparison of response in male mice in control vs under menthol (30 microMolar) incubation. C: comparison of response in female mice in control vs under M8-B (1 microMolar) incubation. D: comparison of response in male mice in control vs under M8-B (1 microMolar) incubation.
File: Figure_3.pzf
Description: Concentration-response curves to different agonists in pudendal arteries in control conditions or incubated with menthol (30 microMolar). A: Contraction to norepinephrine in females. B: Contraction to norepinephrine in males. C: Contraction to serotonin in females. D: Contraction to serotonin in males. E: Percentage of relaxation to histamine in females preconstricted to phenylephrine (1 microMolar). F: Percentage of relaxation to histamine in males preconstricted to phenylephrine (1 microMolar).
File: Figure_4.pzf
Description: Comparison of diameter and vascular reactivity of pudendal arteries from female control vs. female TRPM8 KO mice. A: Diameter of pudendal arteries. B: Contraction elicited by 80 miliMolar KCl solution. C: Concentration-response curve to contraction to norepinephrine. D: Concentration-response curve to percentage of relaxation acetylcholine in arteries precontracted with phenylephrine (1 microMolar).
File: Figure_5.pzf
Description: Concentration-response curve to menthol in segments of thoracic aorta precontracted with phenylephrine (10 microMolar). A: Comparison of menthol percentage of relaxation in aortas with or without endothelium. B: Comparison of menthol percentage of relaxation in aortas of female control vs. female TRPM8 KO mice.
File: Figure_6.pzf
Description: Concentration-response curve to menthol comparing female arteries in the abscence or presence of TRPA1 inhibitor (HC030031, 50 microMolar). A: Comparison of menthol percentage of relaxation in aortas of female control with and without HC030031 precontracted with phenylephrine (10 microMolar). B: Comparison of menthol percentage of relaxation in aortas of female TRPM8 KO mice with and without HC030031 precontracted with phenylephrine (10 microMolar). C: Comparison of menthol percentage of relaxation in pudendal arteries of female TRPM8 KO mice with and without HC030031 precontracted with phenylephrine (1 microMolar).
File: Figure_Supplemental.pzfx
Description: S1: Comparison of male and female pudendal arteries diameter and contractile responsiveness. A: Diameter of pudendal arteries. B: Contraction by 80 miliMolar KCl solution. C: Concentration-response curve to contraction to norepinephrine. D: Concentration-response curve to contraction to serotonin. E: Concentration-response curve to percentage of relaxation of acetylcholine in pudendal arteries precontracted with phenylephrine (1 microMolar). F: Concentration-response curve to percentage of relaxation to histamine in pudendal arteries precontracted with phenylephrine (1 microMolar).
S2: Comparison of acetylcholine percentage of relaxation in aortas with endothelium intact and denuded.
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