Interleukin 1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells.

作者: D Beasley , J H Schwartz , B M Brenner

DOI: 10.1172/JCI115036

关键词: Molecular biologyInterleukinNitric oxideVascular smooth muscleEndocrinologyArginineGUCY1A3Cyclic guanosine monophosphateGUCY1B3ChemistryCycloheximideInternal medicine

摘要: The cytokine interleukin 1 (IL-1) inhibits contractile responses in rat aorta by causing endothelium-independent and prolonged activation of soluble guanylate cyclase. present study tested whether IL-1 activates cyclase inducing production nitric oxide cultured aortic vascular smooth muscle cells (VSMC). induced a marked time-dependent increase cyclic guanosine monophosphate (cGMP) VSMC which was significant at 6 h, increased progressively for up to 36 h. This effect abolished when protein synthesis inhibited with cycloheximide or actinomycin D, suggesting that the involves new synthesis. IL-1-induced cGMP accumulation inhibitors, methylene blue, LY83583, hemoglobin L-arginine analogue NGmonomethyl-L-arginine (L-NMMA). inhibitory L-NMMA reversed 10-fold excess L-arginine, but not D-arginine. Nitrite, an oxidation product oxide, accumulated media incubated 24 h presence whereas both nitrite were attenuated L-arginine-deficient medium. In L-arginine-depleted VSMC, restored control levels 15-min incubation L-arginine. These results demonstrate via pathway dependent on extracellular

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