● ● ● HEMOSTASIS Comment on Isenberg et al, page 1945 Thrombospondin says no to NO

Isenberg and colleagues report that thrombospondin-1 (TSP1) acts as an antago-nist of nitric oxide (NO)–induced vascular relaxation and limits ischemic tissue survival. This finding identifies a newmodulator of vascular contraction and ex-pands the functional repertoire of TSP1. T issue perfusion, a process that is limited inischemic conditions, is mediated by the relaxation of vascular smoothmuscle cells (VSMCs). This process is regulated by the activation of cGMP-dependent kinase leading to themodulation of intracellular Ca2 avail-ability and the activity of myosin light chain (MLC) phosphatase. Contraction requires the binding of Ca2 to calmodulin and the phos-phorylation ofMLC.These interactions con-trol the association between F-actin–contain-ing stress fibers and the contractile protei