Coronary perivascular adipose tissue and K+ channel‐mediated vasodilation in lean and obese hearts (1071.4)

Abstract

This investigation examined the mechanisms by which perivascular adipose tissue (PVAT) influences coronary vasodilation. Coronary arteries from lean and obese Ossabaw swine were isolated, incubated with or without 0.3 g of PVAT for 30 min and pre‐constricted with U46619 (1 μM). In arteries cleaned of PVAT, vasodilation to adenosine (0.01‐30 μM) was decreased ~25% in obese arteries. However, the presence of PVAT attenuated adenosine relaxation ~30% in both lean and obese arteries. Pre‐constriction with KCl (60 mM) abolished coronary dilation to adenosine, suggesting activation of K+ channels. Inhibition of KCa channels with penitrem A (1 μM) impaired responses to adenosine in lean (p<0.001), but not obese (p=0.53), arteries. Dilation to the KCa channel agonist NS‐1619 (30 μM) was attenuated by PVAT in lean, but not obese, arteries. Inhibition of KV7 channels with linopirdine (10 μM) impaired adenosine dilation ~56% in lean arteries. Relaxation to the KV7 channel agonist L364,373 (10 μM) averaged 91 ± 5% in lean arteries vs. 55 ± 8% in obese arteries. Incubation with PVAT diminished vasodilation to L364,373 by ~22% in lean arteries, but had no effect in obese arteries. These findings indicate that while PVAT attenuates adenosine‐mediated vasodilation to a similar extent in lean and obese hearts, the contribution of KCa and KV7 channels to coronary vasodilator responses is markedly impaired in the setting of obesity.Grant Funding Source: Supported by HL117620 and HL092245