Nitric oxide promotes DNA synthesis and cyclic GMP formation in endothelial cells from postcapillary venules.
The nitric oxide (NO)-generating drug sodium nitroprusside (SNP) has been assayed on DNA synthesis in cultured endothelial cells isolated from coronary postcapillary venules of bovine origin (CVEC). DNA synthesis was measured by [3H]-thymidine incorporation following 24 h exposure to SNP (0.1-100 microM). Cyclic GMP levels were also measured following drug exposure. SNP induced a dose-dependent increase in DNA synthesis of CVEC. Maximal effect was observed at 10 microM concentration (44% increment over basal condition). Methylene blue treatment reduced the effect of SNP on thymidine incorporation by 35.4%. After 5 min exposure to SNP, cyclic GMP levels increased up to 3 fold compared to basal. Treatment with N omega-monomethyl-L-arginine (L-NMMA) reduced levels of cyclic GMP to half basal, but did not modify the effect of SNP. Our results show that endogenous and exogenous NO production can modulate proliferation of endothelial cells at microvascular level.
Ziche
M
M
Department of Medical Physiology, Texas A&M University Health Science Center, College Station.
Morbidelli
L
L
Masini
E
E
Granger
H
H
Geppetti
P
P
Ledda
F
F
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels; D006152:Cyclic GMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014699:Venules; D019323:omega-N-Methylarginine
D016222:Fibroblast Growth Factor 2; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004247:DNA; D001120:Arginine; D005996:Nitroglycerin; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; D013936:Thymidine