Thrombospondin-1 null mice exhibit enhanced microvessel endothelium dependent vasodilation, reduced adrenergic sensitivity (676.10)

Thrombospondin-1 null mice exhibit enhanced microvessel endothelium dependent vasodilation, reduced adrenergic sensitivity The extracellular matrix protein thrombospondin -1 (TSP-1), is an antagonist of nitric oxide-mediated vascular relaxation by preventing activation of guanylate cyclase and other downstream targets. Our objective is to determine the effects loss of TSP-1 loss on microvascular reactivity. Arteriolar responses to acetylcholine, phenylephrine, and adenosine, were assessed in skeletal muscle microvasculature of global TSP-1 null (KO) and wildtype (WT) littermate mice using intravital microscopy with the gluteus maximus. KO animals demonstrated 10.7%, 18.6%, 16.5% greater vasodilatory response to acetylcholine concentrations of 10-6, 10-4, and 10-2M (p < 0.05). WT vessels demonstrated more constriction than KO at the highest concentration of phenylephrine, 10-3M (p < 0.05). KO vessels demonstrated greater vasodilatory capacity (p < 0.05), to 10-2M adenosine. WT animals had a 23.8% greater (...