High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes.
Determining the role of vascular receptors in vivo is difficult and not readily accomplished by systemic application of antagonists or genetic manipulations. Here we used intravital microscopy to measure the contributions of sympathetic receptors, particularly α1-adrenoceptor subtypes, to contractil...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3680395?pdf=render |
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| author | Joseph Zacharia Joseph R H Mauban Hema Raina Steven A Fisher Withrow G Wier |
| author_facet | Joseph Zacharia Joseph R H Mauban Hema Raina Steven A Fisher Withrow G Wier |
| author_sort | Joseph Zacharia |
| collection | DOAJ |
| description | Determining the role of vascular receptors in vivo is difficult and not readily accomplished by systemic application of antagonists or genetic manipulations. Here we used intravital microscopy to measure the contributions of sympathetic receptors, particularly α1-adrenoceptor subtypes, to contractile activation of femoral artery in vivo.Diameter and intracellular calcium ([Ca(2+)]i) in femoral arteries were determined by intravital fluorescence microscopy in mice expressing a Myosin Light Chain Kinase (MLCK) based calcium-calmodulin biosensor. Pharmacological agents were applied locally to the femoral artery to determine the contributions of vascular receptors to tonic contraction and [Ca(2+)]i,.In the anesthetized animal, femoral arteries were constricted to a diameter equal to 54% of their passive diameter (i.e. tone = 46%). Of this total basal tone, 16% was blocked by RS79948 (0.1 µM) and thus attributable to α2-adrenoceptors. A further 46% was blocked by prazosin (0.1 µM) and thus attributable to α1-adrenoceptors. Blockade of P2X and NPY1 receptors with suramin (0.5 mM) and BIBP3226 (1.0 µM) respectively, reduced tone by a further 22%, leaving 16% of basal tone unaffected at these concentrations of antagonists. Application of RS100329 (α1A-selective antagonist) and BMY7378 (α1D-selective) decreased tone by 29% and 26%, respectively, and reduced [Ca(2+)]i. Chloroethylclonidine (1 µM preferential for α1B-) had no effect. Abolition of sympathetic nerve activity (hexamethonium, i.p.) reduced basal tone by 90%.Tone of mouse femoral arteries in vivo is almost entirely sympathetic in origin. Activation of α1A- and α1D-adrenoceptors elevates [Ca(2+)]i and accounts for at least 55% of the tone. |
| first_indexed | 2024-12-20T02:15:00Z |
| format | Article |
| id | doaj.art-553b149593464798bcf509a5369ee5ac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:15:00Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-553b149593464798bcf509a5369ee5ac2022-12-21T19:56:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6596910.1371/journal.pone.0065969High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes.Joseph ZachariaJoseph R H MaubanHema RainaSteven A FisherWithrow G WierDetermining the role of vascular receptors in vivo is difficult and not readily accomplished by systemic application of antagonists or genetic manipulations. Here we used intravital microscopy to measure the contributions of sympathetic receptors, particularly α1-adrenoceptor subtypes, to contractile activation of femoral artery in vivo.Diameter and intracellular calcium ([Ca(2+)]i) in femoral arteries were determined by intravital fluorescence microscopy in mice expressing a Myosin Light Chain Kinase (MLCK) based calcium-calmodulin biosensor. Pharmacological agents were applied locally to the femoral artery to determine the contributions of vascular receptors to tonic contraction and [Ca(2+)]i,.In the anesthetized animal, femoral arteries were constricted to a diameter equal to 54% of their passive diameter (i.e. tone = 46%). Of this total basal tone, 16% was blocked by RS79948 (0.1 µM) and thus attributable to α2-adrenoceptors. A further 46% was blocked by prazosin (0.1 µM) and thus attributable to α1-adrenoceptors. Blockade of P2X and NPY1 receptors with suramin (0.5 mM) and BIBP3226 (1.0 µM) respectively, reduced tone by a further 22%, leaving 16% of basal tone unaffected at these concentrations of antagonists. Application of RS100329 (α1A-selective antagonist) and BMY7378 (α1D-selective) decreased tone by 29% and 26%, respectively, and reduced [Ca(2+)]i. Chloroethylclonidine (1 µM preferential for α1B-) had no effect. Abolition of sympathetic nerve activity (hexamethonium, i.p.) reduced basal tone by 90%.Tone of mouse femoral arteries in vivo is almost entirely sympathetic in origin. Activation of α1A- and α1D-adrenoceptors elevates [Ca(2+)]i and accounts for at least 55% of the tone.http://europepmc.org/articles/PMC3680395?pdf=render |
| spellingShingle | Joseph Zacharia Joseph R H Mauban Hema Raina Steven A Fisher Withrow G Wier High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. PLoS ONE |
| title | High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. |
| title_full | High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. |
| title_fullStr | High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. |
| title_full_unstemmed | High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. |
| title_short | High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes. |
| title_sort | high vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1a and α1d adrenoceptor subtypes |
| url | http://europepmc.org/articles/PMC3680395?pdf=render |
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