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Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries

Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance arteries is much less clear. In the present st...

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Autores principales: Kendrick, Dylan J., Mishra, Ramesh C., John, Cini Mathew, Zhu, Hai-Lei, Braun, Andrew P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818784/
https://www.ncbi.nlm.nih.gov/pubmed/35140625
http://dx.doi.org/10.3389/fphys.2021.752366
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author Kendrick, Dylan J.
Mishra, Ramesh C.
John, Cini Mathew
Zhu, Hai-Lei
Braun, Andrew P.
author_facet Kendrick, Dylan J.
Mishra, Ramesh C.
John, Cini Mathew
Zhu, Hai-Lei
Braun, Andrew P.
author_sort Kendrick, Dylan J.
collection PubMed
description Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance arteries is much less clear. In the present study, we have utilized established pharmacological inhibitors of NADPH oxidase activity to examine the potential contribution of ROS to intrinsic myogenic contractility in adult Sprague–Dawley rat resistance arteries and responses to vasoactive agents acting via the endothelium (i.e., acetylcholine, SKA-31) or smooth muscle (i.e., sodium nitroprusside, phenylephrine). In cannulated and pressurized cremaster skeletal muscle and middle cerebral arteries, the NOX inhibitors 2-acetylphenothiazine (2-APT) and VAS2870, selective for NOX1 and NOX2, respectively, evoked concentration-dependent inhibition of basal myogenic tone in a reversible and irreversible manner, respectively, whereas the non-selective inhibitor apocynin augmented myogenic contractility. The vasodilatory actions of 2-APT and VAS2870 occurred primarily via the vascular endothelium and smooth muscle, respectively. Functional responses to established endothelium-dependent and –independent vasoactive agents were largely unaltered in the presence of either 2-APT or apocynin. In cremaster arteries from Type 2 Diabetic (T2D) Goto-Kakizaki rats with endothelial dysfunction, treatment with either 2-APT or apocynin did not modify stimulus-evoked vasoactive responses, but did affect basal myogenic tone. These same NOX inhibitors produced robust inhibition of total NADPH oxidase activity in aortic tissue homogenates from control and T2D rats, and NOX isozymes 1, 2 and 4, along with superoxide dismutase 1, were detected by qPCR in cremaster arteries and aorta from both species. Based on the diverse effects that we observed for established, chemically distinct NOX inhibitors, the functional contribution of vascular NADPH oxidase activity to stimulus-evoked vasoactive signaling in myogenically active, small resistance arteries remains unclear.
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spelling pubmed-88187842022-02-08 Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries Kendrick, Dylan J. Mishra, Ramesh C. John, Cini Mathew Zhu, Hai-Lei Braun, Andrew P. Front Physiol Physiology Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide, are reported to contribute to the dynamic regulation of contractility in various arterial preparations, however, the situation in pressurized, myogenically active resistance arteries is much less clear. In the present study, we have utilized established pharmacological inhibitors of NADPH oxidase activity to examine the potential contribution of ROS to intrinsic myogenic contractility in adult Sprague–Dawley rat resistance arteries and responses to vasoactive agents acting via the endothelium (i.e., acetylcholine, SKA-31) or smooth muscle (i.e., sodium nitroprusside, phenylephrine). In cannulated and pressurized cremaster skeletal muscle and middle cerebral arteries, the NOX inhibitors 2-acetylphenothiazine (2-APT) and VAS2870, selective for NOX1 and NOX2, respectively, evoked concentration-dependent inhibition of basal myogenic tone in a reversible and irreversible manner, respectively, whereas the non-selective inhibitor apocynin augmented myogenic contractility. The vasodilatory actions of 2-APT and VAS2870 occurred primarily via the vascular endothelium and smooth muscle, respectively. Functional responses to established endothelium-dependent and –independent vasoactive agents were largely unaltered in the presence of either 2-APT or apocynin. In cremaster arteries from Type 2 Diabetic (T2D) Goto-Kakizaki rats with endothelial dysfunction, treatment with either 2-APT or apocynin did not modify stimulus-evoked vasoactive responses, but did affect basal myogenic tone. These same NOX inhibitors produced robust inhibition of total NADPH oxidase activity in aortic tissue homogenates from control and T2D rats, and NOX isozymes 1, 2 and 4, along with superoxide dismutase 1, were detected by qPCR in cremaster arteries and aorta from both species. Based on the diverse effects that we observed for established, chemically distinct NOX inhibitors, the functional contribution of vascular NADPH oxidase activity to stimulus-evoked vasoactive signaling in myogenically active, small resistance arteries remains unclear. Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8818784/ /pubmed/35140625 http://dx.doi.org/10.3389/fphys.2021.752366 Text en Copyright © 2022 Kendrick, Mishra, John, Zhu and Braun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Kendrick, Dylan J.
Mishra, Ramesh C.
John, Cini Mathew
Zhu, Hai-Lei
Braun, Andrew P.
Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title_full Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title_fullStr Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title_full_unstemmed Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title_short Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries
title_sort effects of pharmacological inhibitors of nadph oxidase on myogenic contractility and evoked vasoactive responses in rat resistance arteries
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818784/
https://www.ncbi.nlm.nih.gov/pubmed/35140625
http://dx.doi.org/10.3389/fphys.2021.752366
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