Thrombospondin-1 supports blood pressure by limiting eNOS activation and endothelial-dependent vasorelaxation.

ABSTRACT:

Aims

Thrombospondin-1 (TSP1), via its necessary receptor CD47, inhibits nitric oxide (NO)-stimulated soluble guanylate cyclase activation in vascular smooth muscle cells, and TSP1-null mice have increased shear-dependent blood flow compared with wild-type mice. Yet, the endothelial basement membrane should in theory function as a barrier to diffusion of soluble TSP1 into the arterial smooth muscle cell layer. These findings suggested that endothelial-dependent differences in blood flow in TSP1-null mice may be the result of direct modulation of endothelial NO synthase (eNOS) activation by circulating TSP1. Here we tested the hypothesis that TSP1 inhibits eNOS activation and endothelial-dependent arterial relaxation.

Methods and results

Acetylcholine (ACh)-stimulated activati

SUBMITTER: Bauer EM 

PROVIDER: S-EPMC2972685 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature