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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
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Effect of β1 /β2 -adrenoceptor blockade on β3 -adrenoceptor activity in the rat cremaster muscle artery

Samantha L Saunders1, Dana S Hutchinson2, Fiona C Britton3

  • 1Physiology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.

British Journal of Pharmacology
|January 28, 2021
PubMed

Insights

Vascular beta3-adrenoceptors play a role in vasodilation, but their function in rat arteries is inhibited by beta1/beta2-adrenoceptors. Blocking beta1/beta2-adrenoceptors reveals beta3-adrenoceptor mediated vasodilation in skeletal muscle arteries.

Area of Science:

  • Pharmacology
  • Cardiovascular Physiology
  • Adrenoceptor Signaling

Background:

  • The physiological role of vascular beta3-adrenoceptors remains unclear.
  • Cardiac beta3-adrenoceptors are effective after beta1/beta2-adrenoceptor downregulation.
  • Investigating beta3-adrenoceptor interactions in rat arteries is crucial.

Purpose of the Study:

  • To investigate the functional interaction between beta3-adrenoceptors and other beta-adrenoceptor subtypes.
  • To determine the role of beta3-adrenoceptors in rat striated muscle arteries.
  • To elucidate the signaling pathways of beta-adrenoceptors in vascular tone regulation.

Main Methods:

  • Studies utilized cremaster muscle arteries from Sprague-Dawley rats.
  • Beta-adrenoceptor expression was analyzed using RT-PCR and immunofluorescence.
  • Vascular responses to agonists and antagonists were measured via pressure myography.

Main Results:

  • All three beta-adrenoceptor subtypes (β1, β2, β3) were detected in the artery endothelium.
  • Beta3-adrenoceptor agonists (mirabegron, CL 316,243) induced vasodilation only after beta1/beta2-adrenoceptor blockade.
  • SR 58611A potency increased, while isoprenaline responses decreased with beta1/beta2-blockade.

Conclusions:

  • Beta3-adrenoceptor-mediated vasodilation in rat skeletal muscle arteries is evident only upon beta1/beta2-adrenoceptor blockade.
  • Constitutive beta1/beta2-adrenoceptor activity likely inhibits beta3-adrenoceptor function.
  • Findings suggest a complex interplay regulating vascular tone via multiple adrenoceptor subtypes.
Abstract

Keywords:
arteryendotheliumnitric oxideβ-adrenoceptor

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