PERIVASCULAR ADIPOSE TISSUE ALTERS CORONARY ARTERIAL SMOOTH MUSCLE AND ENDOTHELIAL FUNCTION

Abstract

This study tested the hypothesis that perivascular adipose tissue alters the reactivity of coronary vascular smooth muscle and impairs endothelial function. Experiments were conducted in isolated canine coronary arteries and arterioles with and without perivascular adipose tissue. Isometric tension recordings demonstrated that adding adipose tissue to cleaned arteries elicited contractions (active tension 3.95 ± 0.62 g) that were reversed by inhibition of L-type Ca2+ channels with nicardipine (30 μM). Arteries with intact adipose tissue displayed increased contractions to the thromboxane A2 mimetic U46619 and K+ (~ 25% increase). Adipose tissue attenuated endothelial-dependent vasodilation to bradykinin (1 nM – 30 nM), but not acetylcholine. Inhibition of nitric oxide synthase with L-NAME (300 μM) shifted bradykinin-mediated relaxations to the right and eliminated the effect of adipose tissue. Perivascular adipose tissue attenuated bradykinin-induced NO production assessed with amperometric electrodes. There was no difference in dihydroethidium staining of arteries with and without adipose tissue and tempol (10 μM) did not improve endothelial reactivity. In contrast to conduit arteries, adipose tissue had no effect on the resting diameter or bradykinin-induced vasodilation of pressurized coronary arterioles. In conclusion, perivascular adipose tissue contracts coronary arterial smooth muscle via a voltage-dependent mechanism and selectively impairs endothelial-dependent dilation by diminishing NO production. Support HL67804, HL20605.