Perivascular adipose tissue impairs H2O2‐mediated vasodilation in the coronary circulation

Abstract

This investigation examined the effects of perivascular adipose tissue (PVAT) on vasodilatory mechanisms in the coronary circulation. Isometric tension studies were performed on isolated coronary arteries from lean and obese Ossabaw swine. After a 30 min incubation period with 0.3 g PVAT, arteries were constricted with U46619 (1 μM) or PGF2α (10 μM) and responses to H2O2 (1 μM–1 mM) were examined. Compared to untreated‐control arteries, addition of coronary PVAT markedly attenuated relaxation to 1 mM H2O2 in lean swine (78 ± 9% vs. 17 ± 11%). This effect of PVAT was similar in intact and denuded arteries or in arteries pre‐contracted with PGF2α or U46619. However, pre‐constriction with KCl (60 mM) abolished relaxation to H2O2, implicating K+ channels in the vasodilatory response. Inhibition of K+ channels with tetraethylammonium (3 mM), penitrem A (1 μM), barium chloride (30 μM) or glibenclamide (1 μM) did not prevent relaxation to H2O2. In contrast, 4‐aminopyridine (10 mM) prevented relaxation to H2O2 to a similar degree as PVAT. Coronary arteries from obese swine demonstrated similar relaxation to H2O2, however, PVAT did not attenuate this response (98 ± 2% vs. 82 ± 8%, respectively). These findings indicate that coronary PVAT releases factors that diminish coronary vascular smooth muscle vasodilation via inhibition of K+ channels, which is absent in obesity. Support 5T32DK064466–09 and HL092245.