Storage and release of tissue plasminogen activator by sympathetic axons in resistance vessel walls

We studied the immunolocalization of tissue plasminogen activator (t-PA) in rat precapillary arteries, arterioles, and terminal arterioles. Lack of information about the precise location of t-PA within small vessel walls has contributed to uncertainty about its cellular source. The presumed origin has been an endothelial phenotype largely restricted to certain small vessels. However, vessel wall sympathetic axons were recently also shown to store significant amounts of a neuron-generated t-PA in secretory vesicles. Using immunolocalizations we determined the extension of t-PA-bearing axons into the resistance vasculature. Light and confocal images revealed the persistence of t-PA-bearing sympathetic nerve filaments down to the level of 15-microm-diameter terminal arterioles in vasa vasora and the choroidal microvasculature. Immunoelectron localizations confirmed the confinement of t-PA within individual nerve filaments in the deep adventitia. A complete plasminogen activator system (t-PA, plasminogen, and plasmin) was localized in the arteriolar wall matrix. Isolated iris-choroid and mesenteric artery explants from sympathectomized animals released 65 and 43% less t-PA, respectively, than controls. These data support the hypothesis that resistance vessel sympathetic axons release neural t-PA into the wall matrix and the microvascular plasma.