Lack of direct effect of adiponectin on vascular smooth muscle cell BK_Ca channels or Ca²⁺ signaling in the regulation of small artery pressure-induced constriction

Abstract

The aim of this study was to investigate mechanisms by which adiponectin influences vascular Ca2+ signaling, K+ channel activity and thus contractile tone of small arteries. Vasodilation to adiponectin was studied in mesenteric resistance arteries constricted with intraluminal pressure. Ca2+ signals were characterized using high speed confocal microscopy of intact arteries. Patch clamp investigated the effect of adiponectin on individual VSMC potassium (K+) channel currents. Adiponectin dilated arteries constricted with pressure‐induced tone by approximately 5% and the induced vasodilation was only transient. The dilation to adiponectin was reduced by pharmacological interruption of the Ca2+ spark/large conductance activated K+ (BK) channel pathway but from a physiological perspective, interpretation of the data was limited by the small effect. Neither Adiponectin nor the presence of intact perivascular adipose tissue (PVAT) influenced Ca2+ spark or Ca2+ wave frequency or characteristics. Studied using a perforated patch approach, Adiponectin marginally increased current through the VSMC BK channel but this effect was lost using the whole cell technique with dialysis of the cytoplasm. Adiponectin did not change the frequency or amplitude of Ca2+ spark‐induced transient outward currents (STOC). Overall, our study shows that Adiponectin induces only a small and transient dilation of pressure constricted mesenteric arteries. This vasodilatory effect is likely to be independent of Ca2+ sparks or direct BK channel activation.

Perivascular Adipose Tissue: the Sixth Man of the Cardiovascular System

“…Depending on the nature of the study, the interaction between PVAT and different regions of vascular bed, like aorta, mesenteric artery, and coronary artery, were investigated [33,38]. For instance, mouse small mesenteric arteries, together with PVAT, were isolated and mounted on a wire myograph to study how adiponectin activates large conductance calcium-activated potassium (BK ca ) channels or other pathways to induce anti-contractile responses ex vivo [39,40]. PVAT surrounding vasculature consists of many types of cells, dominated by perivascular adipocytes (either brown-like or white-like depending on the region of vascular bed).…”

Adiponectin Decreases Gastric Smooth Muscle Cell Excitability in Mice

“…Recently, other physiological roles of ADPN have emerged including the skeletal muscle sensitivity to this hormone (Krause et al, 2019), the prevention of cardiac dysfunctions (Francisco et al, 2016), and actions on the smooth muscle (AlSaif et al, 2015). Particularly, it has a proved vasorelaxant effect on vascular cells (Hong et al, 2016; Schinzari et al, 2017), and some of the mechanisms by which ADPN influences the contractile tone of small arteries have been clarified (Baylie et al, 2017). Besides vascular muscle activity, ADPN can influence that of the gastric one (Idrizaj et al, 2018a), but no effects of ADPN on the excitability of the SMCs of the gastrointestinal tract are reported at present.…”

“A Step and a Ceiling”: mechanical properties of Ca 2+ spark vasoregulation in resistance arteries by pressure‐induced oxidative activation of PKG

“…We chose the value of 1.26 F/Fo in order to avoid false positives from all of our records. We have published in Physiological Reports previously using this threshold (Baylie et al ) and also in another publication (Khavandi et al ). Increases in Ca 2+ concentration ([Ca 2+ ]) are expressed as F / F o .…”