173P London, UK
Pharmacology 2017

 

 

Perivascular adipose tissue induces relaxation of porcine coronary arteries through release of nitric oxide

M. Saleem, S. Chan, M. Randall. Physiology and Pharmacology, University of Nottingham, Nottingham, United Kingdom.

Introduction: Blood vessels are surrounded by a layer of fat termed perivascular adipose tissue (PVAT), which is receiving interest as a paracrine structure with the capacity to regulate vascular function. Nitric oxide (NO), a soluble gas produced by endothelial cells has recently been reported to be manufactured by PVAT (1). NO may play a significant role in maintenance of vascular tone. This study aimed to investigate the influence of PVAT-derived NO on relaxation of porcine coronary arteries (PCAs).

Method: Cleaned PCA segments with/without PVAT (0.3 g) were mounted for isometric tension studies. Initially, contractions with potassium chloride (KCl) (60 mM) were assessed. Pre-contraction was achieved with U46619 after which, cumulative concentration-response curves to the NO donor sodium-nitroprusside (SNP) (1 pM-3 μM) were constructed. These experiments were repeated in vessels with PVAT with/without inhibition of NO-synthase with N-nitro- L-arginine methyl ester (L-NAME) (300 μM), prior to pre-contraction with U46619. In other experiments, PCAs with PVAT but with denuded endothelium were used, whose responses to KCl were assessed and then L-NAME was added. Griess assay (2) was used to determine the presence of nitrite anion (a stable, non-volatile product of NO) in physiological buffer solution incubated with PCAs (with intact endothelium) and PVAT. Data were analysed by paired, two-tailed Student’s t test.

Results: Vasorelaxation to SNP was significantly potentiated in segments with PVAT compared to those without PVAT (mean ± SEM pEC50: 7.3 ± 0.1 versus 6.7 ± 0.2, p=0.02, n=6). Moreover, experiments in segments with PVAT with/without L-NAME showed significant potentiation of the relaxant responses in vessels exposed to L-NAME (pEC50: 7.4 ± 0.06 versus 6.6 ± 0.04, p<0.0001, n=5). In vessels with PVAT and denuded endothelium, inhibition of NO-synthase caused a significant contraction (mean ± SEM: 6.3 ± 0.7 %) compared to vessels with intact NO-synthase (4.3 ± 0.9 %) (p=0.01, n=6). Production of nitrite was detected in the buffer solution incubated with PVAT (mean ± SEM: 5.9 ± 0.5 nM/mg), although the levels were significantly lower than in the solution incubated with PCAs (16 ± 1.4 nM/mg) (p <0.0001, n=9).

Conclusions: PVAT-derived NO may have contributed to the relaxant effect of exogenous NO derived from SNP. In the condition of impaired endogenous NO synthesis, the sensitivity of vessels to exogenous NO is enhanced leading to augmented vasorelaxation.

References:

(1) Zaborska KE et al. (2016). Int J Obes (Lond) 40: 1205-1214.

(2) Bussey C et al. (2013). Heart 99: A105.