Adiponectin vasodilates small arteries by increasing BK activity

Abstract

We have previously shown that human perivascular adipose tissue (PVAT) vasodilates adjacent arteries, in part by release of adiponectin. This study was designed to further elucidate this adipose‐coupling at a cellular level. Adiponectin caused a small vasodilation of 3rd order mesenteric arteries constricted with pressure‐induced myogenic tone. The vasodilation was substantially reduced by pre‐incubation of arteries with ryanodine (Apn: 5.5%±0.7 vs Apn&Ryr: 2.2%±1, p=0.03). Confocal microscopy of Fluo‐4 loaded mesenteric arteries showed that the presence of intact PVAT increased vascular smooth muscle cell (VSMC) calcium (Ca) spark frequency in mesenteric arteries. However, there was no effect on VSMC Ca spark frequency following incubation with adiponectin. Using patch clamp of mesenteric VSMC, we found that adiponectin significantly increased the BK current when cells were incubated with ryanodine (20μM). Consistent with this, adiponectin increased amplitude but not frequency of spontaneous transient outward currents in untreated cells. Adiponectin had no effect on the Kv component of the whole cell current. It is concluded that adiponectin vasodilates small arteries predominantly by modulating VSMC BK activity, independently of Ca sparks. Intact PVAT appears to have an additive effect by increasing Ca spark frequency, suggesting the contribution of alternative adipose derived vasodilators.