PP.12.12: ELECTRICAL FIELD STIMULATION OF PERIVASCULAR ADIPOSE TISSUE ELICITS A FREQUENCY-DEPENDENT EFFECT ON VESSEL CONTRACTILITY VIA SYMPATHETIC NERVES. (June 2015)

• Record Type: Journal Article
• Authors: Saxton, S.; Watkins, A.; Heagerty, A.M.; Withers, S.
• Is Part Of: Journal of hypertension. Volume 33(2015)Supplement 1
• Publication Date: 2015-06
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000468070.67270.66
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: There is considerable evidence to implicate over-activity of the sympathetic nervous system during obesity and the subsequent development of metabolic syndrome and type 2 diabetes. It has been suggested that these conditions are dependent upon changes in small artery function and type II diabetes. Healthy perivascular fat exerts an anti-contractile effect on circulation which is lost in obesity. Therefore it was decided to examine the effects of sympathetic nerve (SN) stimulation on perivascular adipose tissue (PVAT) function. The hypothesis to be tested was that an anti-contractile factor is released from PVAT as a result of SN stimulation. Design and method: The frequency-stimulation profiles (0.1–30 Hz) of murine mesenteric arteries (<200 μM), +/-PVAT, were characterised using wire myography at various voltages (5–30 V). The accepted test for neural stimulation using 1 μM tetrodotoxin (TTX) was performed, and 1.46 μM 6-hydroxydopamine (6-OHDA) used to sympathetically denervate vessels +/-PVAT. Exogenous PVAT was incubated with TTX and 6-OHDA for 30 minutes before re-suspending in the bath. Specific adrenoceptor stimulation of PVAT function was investigated using noradrenaline, phenylephrine (both 1x10–9–1x10–5 M), and CL-316, 243 (10 μm). Results: At 20&30 V PVAT elicited an anti-contractile effect (P < 0.01); reproducible at 20 V after a 15 minute rest period. Sympathetic denervation of whole vessels with 6-OHDA abolished all significant contractile activity, confirming that EFS at 20 V innervates SNs (P < 0.0001). PVAT incubated with TTX, demonstrated a reduced anti-contractile effect, confirming this effect to be neural and therefore physiologically relevant (P < 0.05). Exogenous PVAT pre-incubated with 6-OHDA also induced a diminished PVAT anti-contractile effect, implicating the role of SNs in PVAT (P < 0.0001). In the noradrenaline but not phenylephrine concentration-response curve, PVAT elicits an anti-contractile response. The addition of CL-316, 243 to phenylephrine-constricted +PVAT vessels induced a relaxation (P < 0.05), indicating the role of beta-3 adrenoceptors. Conclusions: These results clearly demonstrate SN stimulation can provoke the release of vasodilators from PVAT. The mechanism appears to be via activation of the adipocyte membrane located beta-3 adrenoreceptor. Further studies will be carried out in an obese model to understand how over-stimulation leads to a down-regulation and a loss of anti-contractility possibly via beta-3 receptor desensitisation.