Inhibition by triptoquinone-A of LPS- and IL-1 beta-primed induction of NO synthase in rat thoracic aorta.

We investigated the effect of triptoquinone-A (TQA), an active principal of Triptergium wilfordii, on the induction of nitric oxide synthase (NOS) promoted by endotoxin (LPS) and interleukin-1 beta (IL-1 beta). Prophylactic application of TQA selectively prevented LPS-primed initiation of L-arginine (Arg)-induced relaxation, and cGMP formation of rat thoracic aorta, and LPS-stimulated nitrite production by cultured aortic smooth muscle cells, which appear to be mediated by NOS expressed by LPS in vascular smooth muscle. TQA also prevented IL-1 beta-triggered initiation of Arg-induced relaxation and nitrite accumulation. These results suggest that TQA prevents LPS-or IL-1 beta-promoted induction of NOS in vascular smooth muscle, thus inhibiting development of Arg-induced vasorelaxation.

[1]  C. Thiemermann,et al.  Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo. , 1993, European journal of pharmacology.

[2]  B. Brenner,et al.  Interleukin 1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. , 1991, The Journal of clinical investigation.

[3]  H. Moritoki,et al.  Nitric oxide synthase responsible for l‐arginine‐induced relaxation of rat aortic rings in vitro may be an inducible type , 1992, British journal of pharmacology.

[4]  P. Belloni,et al.  Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. , 1990, Journal of the National Cancer Institute.

[5]  K. Shishido,et al.  Tripterygium wilfordii var. regelii which are interleukin-1 inhibitors , 1994 .

[6]  P. Libby,et al.  Inducible interleukin-1 gene expression in human vascular smooth muscle cells. , 1986, The Journal of clinical investigation.

[7]  S. Moncada,et al.  Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. , 1990, Biochemical and biophysical research communications.

[8]  L. Davis,et al.  Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human immune responsiveness. , 1991, Arthritis and rheumatism.

[9]  T. Mckenna,et al.  Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility. Association with vascular cytokine release. , 1990, The Journal of clinical investigation.