Role of Perivascular Adipose Tissue in Endothelial Function of Porcine Coronary Artery

Perivascular adipose tissue (PVAT), the exterior covering layer of most blood vessels, is receiving interest as a paracrine structure secreting various vasoactive agents. Most conventional pharmacological studies carefully dissect off the adherent adipose tissue and so this aspect of vascular control is often neglected (1). Arterial tone is dependent on the effects of endothelium-derived nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH) (2). This study aimed to determine the influence of PVAT on endothelium-dependent vaso relaxation induced by bradykinin (BK) in porcine coronary arteries (PCAs).

PCAs (of either sex) were mounted for isometric tension studies in organ-bath set ups. Initially, baseline contraction with potassium chloride (KCl) (60 mM) was assessed. Thirty minutes later, NO synthase and cyclooxygenase were inhibited with L-NAME (N-nitro L-arginine methyl ester) (300 µM) and indomethacin (10 µM) respectively. Pre-contraction was achieved with U46619 (a thromboxane A2 mimetic),immediately after which, concentration-response curves to BK (0.1 nM – 10 µM) were constructed. The experiments were then extended by the additional presence of candesartan (10 µM) (to block the angiotensin II, type I: AT1 receptor), followed by assessment of BK-induced vaso relaxation. Data were analysed by unpaired, two-tailed Student’s t test for comparison of two groups and ANOVA followed by Bonferroni’s post-hoc test for comparison of multiple groups.

In female and male PCAs, a comparison of the contractile response to KCl (60mM) in segments with PVAT to those without PVAT showed that the response was significantly reduced in the segments with PVAT (p<0.05). In female PCAs, it was observed that the endothelium-dependent relaxant responses in the segments with PVAT were significantly reduced (Rmax = 15.9 ± 6.4%; pEC50 = 8.5 ± 1.4; n = 6) in comparison to the segments without PVAT, in the presence of L-NAME and indomethacin (Rmax = 58.2 ± 2.4 %; pEC50 = 9.9 ± 0.7; n = 6) (p<0.0001) and in comparison to the segments with PVAT only (Rmax = 61.7 ± 4.8 %; pEC50 = 9.8 ± 0.2; n = 6) (p<0.0001). On investigation of female PCAs in the additional presence of candesartan, it was observed that the relaxant responses to BK were no longer significantly inhibited in the segments with PVAT, compared to the control segments with and without PVAT (n=5). In male PCAs, in the presence of L-NAME and indomethacin, the segments with PVAT were not suppressed compared to the segments without PVAT (n=8). Additional inhibition of the male vessels with candesartan showed no significant difference in the responses to BK in the segments with and without PVAT (n=5).

In conclusion, the contractile response to KCl may have been inhibited by the release of a relaxant factor from PVAT. In female PCAs, a contractile factor, possibly angiotensin II, may have been released by PVAT which suppressed the relaxant response to BK, while the NO and prostacyclin mechanisms were inhibited. Hence, PVAT derived angiotensin II maybe interfering with EDH-mediated relaxation.

(1) Szasz T and Webb RC (2012). Clin Sci 122: 1–12.

(2) Feletou M (2009). Br J Pharmacol 156: 545-562.