POSSIBLE INVOLVEMENT OF TYROSINE KINASE IN THE LPS-PROMOTED INITIATION OF L-ARGININE-INDUCED RELAXATION OF RAT AORTA MEDIATED BY INDUCTION OF NO SYNTHASE

Tyrosine kinase inhibitors herbimycin A, genistein and erbstatin analog prevented endotoxin (LPS)-promoted initiation of L-arginine (Arg)-induced relaxations and cGMP formation in rat thoracic aorta, which appear to be mediated by nitric oxide synthase expressed by LPS in the vascular smooth muscle. Similarly, interleukin-1 beta (IL-1 beta) triggered initiation of Arg-induced relaxation of the arteries. In addition, in the aortic smooth muscle cells cultured in the presence of Arg, LPS- or IL-1 beta-triggered accumulation of nitrite was suppressed by the tyrosine kinase inhibitors. These results suggest that tyrosine kinase is involved in the LPS- and IL-1 beta-promoted induction of nitric oxide synthase in the vascular smooth muscle, which in turn mediates production of NO from added Arg, thus stimulating formation of cGMP and causing relaxation. Alternatively, it is possible that LPS acts indirectly through cytokines such as IL-1 beta.