Perivascular adipose tissue (PVAT) and the sympathetic nervous system (SNS) both regulate vascular tone. Healthy PVAT is a potent paracrine tissue that exerts an anti-contractile effect in response to agonist-induced constriction. Although there are many known factors expressed and released by PVAT, this anti-contractile effect has been proposed to be due to the release of an unidentified adipose-derived relaxing factor (ADRF). This study investigated the effect of electrical field stimulation (EFS) on PVATs anti-contractile activity.Methods
The effect of EFS on the contractility of isolated Sprague-Dawley rat mesenteric arteries (approx. 250–300 µm internal diameter) both with and without PVAT was investigated using wire myography. Contractile responses to increasing frequencies of EFS (2–100Hz, 20V, 0.2 ms pulse width, 3s duration) were measured in the response to the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) (1.46 mmol/L and 0.02 mmol/L glutathione in 1M HEPES). Exogenous PVAT was also dissected from the mesenteric bed and placed in close proximity to arteries lacking PVAT and contractile responses to EFS were measured. Concentration response curves to noradrenaline (NA) (1 × 10–9 – 3 × 10–5M) were generated. Data were analysed by two-way ANOVA.Results
PVAT exerted an anti-contractile effect on the contractile response to EFS (PVAT vs. No PVAT, p < 0.0001, n = 4). This was also observed with exogenous PVAT (No PVAT vs. Ex. PVAT, p < 0.0001, n = 2) suggesting that the PVAT anti-contractile effect was not due to vessel insulation but the secretion of an unidentified ADRF. Destruction of intramural nerves within the vessel and PVAT using 6-OHDA abolished all EFS-mediated constriction (PVAT/6-OHDA vs. No PVAT, p < 0.0001, n = 2). Destruction of only PVAT intramural nerves abolished the anti-contractile effect (Ex. PVAT/6-OHDA vs. PVAT, p < 0.0002, n = 2). In the presence of PVAT vasoconstriction in response to NA was reduced (PVAT vs. No PVAT, p = 0.0028, n = 9).Conclusions
Overall, these data suggest a role for SNS activation of PVAT in mediating the anti-contractile effect.