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High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via ?1A- and ?1D-adrenoceptor subtypes.

ABSTRACT:

Background and purpose

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 ?1-adrenoceptor subtypes, to contractile activation of femoral artery in vivo.

Experimental approach

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,.

Key results

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 ?2-adrenoceptors. A further 46% was blocked by prazosin (0.1 µM) and thus attributable to ?1-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 (?1A-selective antagonist) and BMY7378 (?1D-selective) decreased tone by 29% and 26%, respectively, and reduced [Ca(2+)]i. Chloroethylclonidine (1 µM preferential for ?1B-) had no effect. Abolition of sympathetic nerve activity (hexamethonium, i.p.) reduced basal tone by 90%.

Conclusion and implications

Tone of mouse femoral arteries in vivo is almost entirely sympathetic in origin. Activation of ?1A- and ?1D-adrenoceptors elevates [Ca(2+)]i and accounts for at least 55% of the tone.

SUBMITTER: Zacharia J

PROVIDER: S-EPMC3680395 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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High vascular tone of mouse femoral arteries in vivo is determined by sympathetic nerve activity via α1A- and α1D-adrenoceptor subtypes.

Zacharia Joseph J Mauban Joseph R H JR Raina Hema H Fisher Steven A SA Wier Withrow G WG

PloS one 20130612 6

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Diameter and intracellular calcium ([Ca(2+)]i) in femoral arteries were determined by intravital flu ...[more]

PMID: 23776582

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