Microvascular Endothelial Dysfunction in Obesity Is Driven by Macrophage-Dependent Hydrogen Sulfide Depletion.

OBJECTIVE: The function of perivascular adipose tissue as an anticontractile mediator in the microvasculature is lost during obesity. Obesity results in inflammation and recruitment of proinflammatory macrophages to the perivascular adipose tissue that is paralleled by depletion of the vasorelaxant signaling molecule hydrogen sulfide (H2 S) in the vessel. The current objective was to assess the role of macrophages in determining vascular [H2 S] and defining how this impinged on vasodilation.

APPROACH AND RESULTS: Contractility and [H2 S] were measured in mesenteric resistance arterioles from lean and obese mice by using pressure myography and confocal microscopy, respectively. Vasodilation was impaired and smooth muscle and endothelial [H2 S] decreased in vessels from obese mice compared with those from lean controls. Coculturing vessels from lean mice with macrophages from obese mice, or macrophage-conditioned media, recapitulated obese phenotypes in vessels. These effects were mediated by low molecular weight species and dependent on macrophage inducible nitric oxide synthase activity.

CONCLUSIONS: The inducible nitric oxide synthase activity of perivascular adipose tissue-resident proinflammatory macrophages promotes microvascular endothelial dysfunction by reducing the bioavailability of H2 S in the vessel. These findings support a model in which vascular H2 S depletion underpins the loss of perivascular adipose tissue anticontractile function in obesity.