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. 2022 Jan 3;36(2):191–201. doi: 10.1177/02698811211055811

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© The Author(s) 2022

This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Figure 3. — Concentration-dependent vasodilator response of thoracic aorta ring preparations in the absence (control) and presence of antipsychotic drugs (bars represent SEM). (a) Haloperidol (1 µM) showed no effect on endothelium-dependent vasodilation to acetylcholine (n = 6, p > 0.05, two-way ANOVA); (b) analysis by two-way ANOVA showed for 1 µM aripiprazole (n = 10, *p = 0.0199) and 0.5 µM olanzapine (n = 6, ^#p = 0.0001) a small but significant rightward shift but no effect on maximal vasodilation (p > 0.05, Sidak multiple comparison test); (c) Clozapine (1 µM) induced a strong rightward shift of the concentration-response curve to acetylcholine (n = 8, *p < 0.0001, two-way ANOVA) and a significantly weaker maximal relaxation (^#p < 0.0001, Sidak multiple comparison test); (d) Clozapine showed no effect on vasodilation to the NO-donor DEA/NO at any concentration (n = 6, p > 0.05, Sidak multiple comparison test following two-way ANOVA); (e) the aryl hydrocarbon receptor antagonist CH223191 (10 µM) significantly improved vasodilation (n = 6, *p < 0.0001, two-way ANOVA) and the maximal vasodilator response to acetylcholine in the presence of clozapine (^#p = 0.0033, Sidak multiple comparison test). In addition, CH223191 improved vasodilation to acetylcholine in the absence of clozapine (n = 6, *p < 0.0001, two-way ANOVA), but did not alter the maximal vasodilator response (p > 0.05, Sidak multiple comparison test). (f) In contrast to C57BL6 mice, clozapine (1 µM) showed a lesser, albeit still significant (p < 0.001, two-way ANOVA), rightward shift of the concentration-response curve to acetylcholine in AhR-deficient mice (AhR^-/-) and no effect on maximal vasodilation (p > 0.05, Sidak multiple comparison test).