The induction of nitric oxide synthase activity is inhibited by TGF-β1, PDGF(AB) and PDGF(BB) in vascular smooth muscle cells

Abstract

The effect of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was investigated on the induction of nitric oxide synthase activity caused by interleukin-1β in cultured smooth muscle cells from rat aorta. TGF-β1, PDGF(AB) and PDGF(BB) but not PDGF(AA) inhibited in a concentration-dependent manner the production of nitrite, an oxidation product of nitric oxide, evoked by interleukin-1β. The growth factors alone did not stimulate the release of nitrite. The addition of interleukin-1β-treated smooth muscle cells to suspensions of indomethacin-treated human washed platelets inhibited the aggregation evoked by thrombin whereas no effect was observed with untreated cells. Platelet aggregation was not inhibited by smooth muscle cells that had been pretreated with interleukin-1β in combination with either TGF-β1, PDGF(AB) or PDGF(BB) but not with PDGF(AA). These observations demonstrate that platelet-derived products such as TGF-β and PDGFs inhibit the induction of nitric oxide synthase activity in vascular smooth muscle cells.