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

Abstract

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 (p < 0.05) vasoconstriction in response to the highest dose of phenylephrine, 10‐3M. KO animals demonstrated a 23.5% higher (p < 0.05) maximal dilatory capacity in response to 10‐2M adenosine than WT. These data provide evidence that TSP‐1 is an important physiologic regulator of skeletal muscle microvascular reactivity.