Open Access

Philip Poley, Peter M. Benz, Cor de Wit

• VASP is a member of the Enabled/VASP protein family that is involved in cortical actin dynamics and may also contribute to the formation of gap junctions. In vessels, gap junctional coupling allows the transfer of signals along the vessel wall and coordinates vascular behavior. Moreover, VASP is reportedly a mediator of NO-induced inhibition of platelet aggregation. Therefore, we hypothesized that VASP exerts also important physiologic functions in arterioles. We examined the spread of vasodilations enabled by gap junctional coupling in endothelial cells as well as NO-induced arteriolar dilations in VASP-deficient mice by intravital microscopy of the microcirculation in a skeletal muscle in anesthetized mice. Conducted dilations were initiated by brief, locally confined stimulation of the arterioles with acetylcholine. The maximal diameters of the arterioles under study ranged from 30 to 40 μm. Brief stimulation with acetylcholine induced a short dilation at the local site that was also observed at remote, upstream sites without an attenuation of the amplitude up to a distance of 1.2 mm in control animals (wild-type). In contrast, remote dilations were reduced in VASP-deficient mice despite a similar local dilation indicating an impairment of conducted dilations. Superfusion of NOdonors induced a concentration-dependent dilation in wild-type mice. However, these dilations were slightly reduced in VASP-deficient animals. In contrast, dilations induced by the endothelial stimulator acetylcholine were fully preserved in VASP-deficient mice. In summary, this study suggests that VASP exerts critical functions in arteriolar diameter control. It is crucial for the conduction of dilator signals along the endothelial cell layer. The impairment possibly reflects a perturbed formation of gap junctions in the endothelial cell membrane. VASP also participates in the full dilatory potential of NOdonors although the effect of its deficiency is only subtle. In contrast, VASP is not required for dilations initiated by endothelial stimulation which are mediated in the murine microcirculation by an EDH-mechanism.