Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells.
Effects of nitric oxide (NO) and NO-producing vasodilators such as glyceryl trinitrate and sodium nitroprusside were tested on DNA synthesis in the clonal rat aortic smooth muscle cells, RACS-1. DNA synthesis was estimated by [3H]thymidine incorporation to DNA. NO and NO-producing vasodilators inhibited the DNA synthesis that was induced by 10% fetal calf serum. NO and NO-producing vasodilators also inhibited the basal level of DNA synthesis that occurred possibly as a result of autocrine mechanisms. NO-producing vasodilators also inhibited the fetal calf serum-induced proliferation of cells. Sodium nitroprusside inhibited the endothelin-mediated DNA synthesis. In another mesenchymal cell line, Chinese hamster fibroblast V79 cells, NO and NO-producing vasodilators failed to inhibit DNA synthesis, excluding the possibility of general cell toxicity. An exposure to NO and NO-producing vasodilators resulted in an increase of cyclic GMP (cGMP) content in the RACS-1 cells. A cGMP analog, 8-bromo-cGMP, inhibited DNA synthesis in the RACS-1 cells. These results suggest that EDRF/nitric oxide released from endothelium possibly contributes to inhibition of the DNA synthesis in vascular smooth muscle cells.
Nakaki
T
T
Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
Nakayama
M
M
Kato
R
R
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006152:Cyclic GMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis*; D016232:Endothelins / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D014665:Vasodilator Agents; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D004247:DNA; D005996:Nitroglycerin; D006152:Cyclic GMP