Noradrenergic Receptor Function In Healthy And Obese Perivascular Adipose Tissue

Perivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating blood pressure. Evidence suggests that the sympathetic nervous stimulation of PVAT triggers the release of anti-contractile factors via activation of beta 3 -adrenoceptors. There is considerable evidence of sympathetic over-activity in obesity, which could result in the loss of PVAT function, and subsequent hypertension. Therefore it was decided to examine beta 3 -adrenoceptor function in obesity. Electrical field stimulation (EFS) profiles of healthy and obese mouse mesenteric arteries ( 3- adrenoceptor function was investigated using the agonist CL-316,243 (10uM) and antagonist SR59203A (100nM). The role of the vasodilator nitric oxide (NO) was studied using nitric oxide synthase (NOS) inhibitor L-NMMA (100uM), and NOS activator histamine (100uM). During EFS healthy PVAT elicits an anti-contractile effect (n = 8, P 3- adrenoceptors in healthy PVAT using SR59230A significantly reduced the anti-contractile effect (n = 8, P 3- adrenoceptors in obese PVAT using CL-316,243 did not restore function (n = 7, P = 0.77). Solution transfer from stimulated healthy exogenous PVAT to a -PVAT vessel significantly reduced contraction (n = 8, P These results demonstrate that in health PVAT releases an anti-contractile factor via activation of beta 3 -adrenoreceptors, which downstream trigger the release of NO. In obesity, the anti-contractile effect is lost and cannot be restored by beta 3 -adrenoceptor activation, but is restored by activation of NOS. This suggests that in obesity beta 3 -adrenoreceptors must be downregulated or desensitised, leading to a loss of anti-contractile function, which may contribute to the development of hypertension.