Journal article
Effect of β1/ β2 -adrenoceptor inhibition on β3 -adrenoceptor activity in the rat cremaster muscle artery
British Journal of Pharmacology, Vol.178(8), pp.1789-1804
2021
PMID: 33506492
Abstract
BACKGROUND AND PURPOSE: The physiological role of vascular β3 -adrenoceptors (β3 -ARs) is not fully understood. Recent evidence suggests cardiac β3 -AR are functionally effective only after down-regulation of β1 /β2 -ARs. This study investigated the functional interaction between the β3 -AR and other β-AR subtypes in rat striated muscle arteries. EXPERIMENTAL APPROACH: Studies were performed in cremaster muscle arteries isolated from male Sprague-Dawley rats. β-AR expression was assessed through rt-PCR and immunofluorescence (IF). Functional effects of β3 -AR agonists and antagonists and other β-AR ligands were measured with pressure myography. KEY RESULTS: All three β-AR subtypes were present in the endothelium of the rat cremaster muscle artery. The β3 -AR agonists mirabegron and CL316,243 had no effect on the diameter of rat pressurized (70 mmHg) cremaster muscle arterioles with myogenic tone, while the β3 -AR agonist SR58611A and the non-selective β-AR agonist isoprenaline caused concentration-dependent dilation. In the presence of β1/2 -AR antagonists including nadolol (10 μM), atenolol (1 μM) and ICI 118,551 (0.1 μM), mirabegron and CL316,243 were effective in causing vasodilation and the potency of SR58611A was enhanced, while responses to isoprenaline were inhibited. The β3 -AR antagonist L748,337 (1 μM) inhibited vasodilation caused by β3 -AR agonists (in the presence of β1/2 -AR blockade), but L748,337 had no effect on isoprenaline-induced vasodilation. CONCLUSION AND IMPLICATIONS: All three β-AR subtypes were present in the endothelium of the rat cremaster muscle artery, but β3 -AR-mediated vasodilation was only evident after blockade of β1/2 -ARs. This suggests constitutive β1/2 -AR activity inhibits β3 -AR function in the endothelium of skeletal muscle resistance arteries.
Details
- Title
- Effect of β1/ β2 -adrenoceptor inhibition on β3 -adrenoceptor activity in the rat cremaster muscle artery
- Authors
- Samantha L Saunders (Author) - UNSW AustraliaDana S Hutchinson (Author) - Monash UniversityFiona C Britton (Author) - University of Nevada, Las VegasLu Liu (Author) - UNSW AustraliaIrit Markus (Author) - UNSW AustraliaShaun Sandow (Author) - University of the Sunshine Coast, Queensland, School of Health and Sport Sciences - LegacyTimothy V Murphy (Corresponding Author) - UNSW Australia
- Publication details
- British Journal of Pharmacology, Vol.178(8), pp.1789-1804
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2021
- DOI
- 10.1111/bph.15398
- ISSN
- 1476-5381
- PMID
- 33506492
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99508608502621
- Output Type
- Journal article
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