Summary
Proteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor
peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked
by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically
inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and
diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory
effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated
vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed
detector blood vessels. These relaxations were abolished by the inhibitor of nitric
oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated
cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase
mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin.
These results demonstrate that thrombin regulates the expression of the inducible
nitric oxide synthase at a transcriptional level via the proteolytic activation of
the thrombin receptor in vascular smooth muscle cells
