Platelets Inhibit the Induction of Nitric Oxide Synthesis by Interleukin-1β in Vascular Smooth Muscle Cells

Abstract

AbstractWe have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1β (IL-1β) -treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1β resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1β-mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1β-treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1β-treated smooth muscle cells to suspensions of platelets inhibited their thrombininduced aggregation. The simultaneous treatment of smooth muscle cells with IL-1β and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1β-induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1β-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downreg-ulate the production of nitric oxide by IL-1β-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.