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Text
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URL Address
<a href="http://doi.org/10.1152/ajpheart.00082.2011" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpheart.00082.2011</a>
Pages
H1135–1142
Issue
3
Volume
301
Dublin Core
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Title
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Endothelin-mediated in vivo pressor responses following TRPV1 activation.
Publisher
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American journal of physiology. Heart and circulatory physiology
Date
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2011
2011-09
Subject
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*Blood Pressure/drug effects; *Vasoconstriction/drug effects; Adrenergic alpha-Agonists/administration & dosage; Analysis of Variance; Animal; Animals; Azepines/administration & dosage; Biphenyl Compounds/administration & dosage; Capsaicin/administration & dosage; Cells; Cultured; Diabetes Mellitus; Diabetic Angiopathies/genetics/*metabolism/physiopathology; Dipeptides/administration & dosage; Disease Models; Dose-Response Relationship; Drug; Endothelial Cells/metabolism; Endothelin A Receptor Antagonists; Endothelin A/metabolism; Endothelin B Receptor Antagonists; Endothelin B/metabolism; Endothelin-1/*metabolism; Enzyme-Linked Immunosorbent Assay; Femoral Artery/drug effects/*metabolism/physiopathology; Inbred C57BL; Indoles/administration & dosage; Infusions; Intravenous; Knockout; Male; Mice; Phenylephrine/administration & dosage; Receptor; TRPV Cation Channels/agonists/deficiency/genetics/*metabolism; Type 2/genetics/*metabolism/physiopathology; Vasoconstrictor Agents/administration & dosage
Creator
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Ohanyan Vahagn A; Guarini Giacinta; Thodeti Charles K; Talasila Phani K; Raman Priya; Haney Rebecca M; Meszaros J Gary; Damron Derek S; Bratz Ian N
Description
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Transient receptor potential vanilliod 1 (TRPV1) channels have recently been postulated to play a role in the vascular complications/consequences associated with diabetes despite the fact that the mechanisms through which TRPV1 regulates vascular function are not fully known. Accordingly, our goal was to define the mechanisms by which TRPV1 channels modulate vascular function and contribute to vascular dysfunction in diabetes. We subjected mice lacking TRPV1 [TRPV1((-/-))], db/db, and control C57BLKS/J mice to in vivo infusion of the TRPV1 agonist capsaicin or the alpha-adrenergic agonist phenylephrine (PE) to examine the integrated circulatory actions of TRPV1. Capsaicin (1, 10, 20, and 100 mug/kg) dose dependently increased MAP in control mice (5.7 +/- 1.6, 11.7 +/- 2.1, 25.4 +/- 3.4, and 51.6 +/- 3.9%), which was attenuated in db/db mice (3.4 +/- 2.1, 3.9 +/- 2.1, 7.0 +/- 3.3, and 17.9 +/- 6.2%). TRPV1((-/-)) mice exhibited no changes in MAP in response to capsaicin, suggesting the actions of this agonist are specific to TRPV1 activation. Immunoblot analysis revealed decreased aortic TRPV1 protein expression in db/db compared with control mice. Capsaicin-induced responses were recorded following inhibition of endothelin A and B receptors (ET(A) /ET(B)). Inhibition of ET(A) receptors abolished the capsaicin-mediated increases in MAP. Combined antagonism of ET(A) and ET(B) receptors did not further inhibit the capsaicin response. Cultured endothelial cell exposure to capsaicin increased endothelin production as shown by an endothelin ELISA assay, which was attenuated by inhibition of TRPV1 or endothelin-converting enzyme. TRPV1 channels contribute to the regulation of vascular reactivity and MAP via production of endothelin and subsequent activation of vascular ET(A) receptors. Impairment of TRPV1 channel function may contribute to vascular dysfunction in diabetes.
Identifier
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<a href="http://doi.org/10.1152/ajpheart.00082.2011" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00082.2011</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Blood Pressure/drug effects
*Vasoconstriction/drug effects
2011
Adrenergic alpha-Agonists/administration & dosage
American journal of physiology. Heart and circulatory physiology
Analysis of Variance
Animal
Animals
Azepines/administration & dosage
Biphenyl Compounds/administration & dosage
Bratz Ian N
Capsaicin/administration & dosage
Cells
Cultured
Damron Derek S
Department of Integrative Medical Sciences
Diabetes Mellitus
Diabetic Angiopathies/genetics/*metabolism/physiopathology
Dipeptides/administration & dosage
Disease Models
Dose-Response Relationship
Drug
Endothelial Cells/metabolism
Endothelin A Receptor Antagonists
Endothelin A/metabolism
Endothelin B Receptor Antagonists
Endothelin B/metabolism
Endothelin-1/*metabolism
Enzyme-Linked Immunosorbent Assay
Femoral Artery/drug effects/*metabolism/physiopathology
Guarini Giacinta
Haney Rebecca M
Inbred C57BL
Indoles/administration & dosage
Infusions
Intravenous
Knockout
Male
Meszaros J Gary
Mice
NEOMED College of Medicine
Ohanyan Vahagn A
Phenylephrine/administration & dosage
Raman Priya
Receptor
Talasila Phani K
Thodeti Charles K
TRPV Cation Channels/agonists/deficiency/genetics/*metabolism
Type 2/genetics/*metabolism/physiopathology
Vasoconstrictor Agents/administration & dosage