The influence of beta-adrenoceptors and perivascular adipose tissue in modulating vascular function

Katie Hood1, Emma Pottinger1, Steven Edwards1, Craig Daly1, Ian McGrath1, Janette Bulloch2. 1The University of Glasgow, Glasgow, UK, 2The University of the West of Scotland, Hamilton, UK.

The perivascular adipose tissue (PVAT) surrounding most blood vessels is known to release a variety of adipokines which can be either pro- or anti-atherogenic (Zhang & Zhang, 2009). A modulating effect of PVAT on the vasculature has been reported (Soltis & Cassis, 1991) but the exact mechanism and receptors involved in the release of factors from PVAT and effects of these factors on the different components of the vascular wall have to be fully examined. The effects of PVAT on vascular contractions in mouse thoracic aorta were examined using wire myography. Noradrenaline, adrenaline and 5-Hydroxytryptamine were utilised as contractile agonists in vessels with and without PVAT. Cumulative concentration response curves were then constructed and paired t-tests were performed. As the reports of a widespread distribution of beta - adrenoceptors (Daly & McGrath, 2011) extend to the presence of beta3-adrenoceptors on adipose tissue such as PVAT, the selective beta3-adrenoceptor agonist BRL 37344 was employed to test whether a functional presence can be shown.

In the mouse thoracic aorta we now show that vasoconstrictor responses to the catecholamines noradrenaline and adrenaline are reduced in the presence of PVAT, particularly at low concentrations of these agonists. However, responses to serotonin (5HT) (1x10-8M- 1x10-5M) which were antagonised by ketanserin (3x10-8M-3x10-7M) at lower agonist doses and by a combined phentolamine (1μM) propranolol (1μM) pre-treatment at higher doses, were either enhanced or unaffected in the presence of PVAT indicating that the layer of fat is not just simply acting as a barrier (or sponge) to exogenously applied agonist. In the presence of 5HT (3x10-5M) induced contraction, the subsequent administration of isoprenaline (1x10-7M - 3x10-5M) and BRL 37344 (3x10-8M - 3x10-5M) produced concentration dependent relaxations which were blocked following combined phentolamine (1μM) and propranolol pre-treatment (1μM). The responses to BRL 37344 (3x10-8M - 3x10-7M) were reduced in vessels were PVAT had been removed.

We thus conclude that there is a functional beta3-adrenoceptor on mouse aortic PVAT and that the presence of PVAT differentially influences the responses to agonists on the blood vessel with adrenoceptor-mediated responses being reduced and those mediated by 5HT2 enhanced.

Zhang H & Zhang C (2009) Am J Biomed SCi 1(2): 133, 1-13

Soltis & Cassis (1991) Clin Exp Hypertens. 13, 277-289.

Daly CJ & McGrath JC (2011). "Previously unsuspected widespread cellular and tissue distribution of beta-adrenoceptors and its relevance to drug action" Trends in Pharmacological Sciences. April 2011, 32 (4), 219-226.

K. Hood would like to thank the Physiological Society for a Vacation Studentship award which enabled completion of this study.