Mooradian D L, Hutsell T C, Keefer L K
Department of Laboratory Medicine and Pathology/Biomedical Engineering Center, University of Minnesota, Minneapolis 55455-0392, USA.
J Cardiovasc Pharmacol. 1995 Apr;25(4):674-8.
Nitric oxide (NO) inhibits vascular smooth muscle cell (SMC) growth in vitro. To determine the effects of release rate and exposure time on SMC growth inhibition by NO, we compared the activities of five NO donors that generate NO with half-lives of 2 min (DEA/NO, Et2N[N2O2]Na), 15 min (PAPA/NO, CH3(CH2)2N[N2O2]-(CH2)3NH3+), 39 min, (SPER/NO, H2N(CH2)3NH2+(CH2)4N[N2O2]-(CH2)3NH2), 3 h (DPTA/NO, H2N(CH2)3N[N2O2]-(CH2)3NH3+), and 20 h (DETA/NO, H2N(CH2)2N[N2O2]-(CH2)2NH3+). After 22-h treatment, rat aorta SMC (RA-SMC) DNA synthesis was inhibited with IC50 values of 180, 60, and 40 microM for SPER/NO, DPTA/NO, and DETA/NO, respectively. DEA/NO and PAPA/NO did not inhibit DNA synthesis significantly at any concentration tested (20-500 microM). The inhibitory effect of NO on RA-SMC DNA synthesis was thus greatest when a given molar dose of NO was delivered slowly throughout the 22-h period. The antiproliferative effect of DETA/NO was confirmed by measurement of cell numbers for 7 days. When RA-SMC were treated with 500 microM DETA/NO on days 1, 3, and 5, growth was completely suppressed. Cell viability was > 95%, confirming that DETA/NO was not cytotoxic. The results suggest that NO donors may be useful inhibitors of intimal hyperplasia and restenosis after vascular injury such as balloon angioplasty.
一氧化氮（NO）在体外可抑制血管平滑肌细胞（SMC）的生长。为了确定释放速率和暴露时间对NO抑制SMC生长的影响，我们比较了五种NO供体的活性，这些供体产生的NO半衰期分别为2分钟（DEA/NO，Et2N[N2O2]Na）、15分钟（PAPA/NO，CH3(CH2)2N[N2O2]-(CH2)3NH3+）、39分钟（SPER/NO，H2N(CH2)3NH2+(CH2)4N[N2O2]-(CH2)3NH2）、3小时（DPTA/NO，H2N(CH2)3N[N2O2]-(CH2)3NH3+）和20小时（DETA/NO，H2N(CH2)2N[N2O2]-(CH2)2NH3+）。经过22小时的处理后，大鼠主动脉SMC（RA-SMC）的DNA合成受到抑制，SPER/NO、DPTA/NO和DETA/NO的IC50值分别为180、60和40微摩尔。在任何测试浓度（20-500微摩尔）下，DEA/NO和PAPA/NO均未显著抑制DNA合成。因此，当在整个22小时内缓慢释放给定摩尔剂量的NO时，NO对RA-SMC DNA合成的抑制作用最大。通过测量7天的细胞数量证实了DETA/NO的抗增殖作用。当在第1、3和5天用500微摩尔DETA/NO处理RA-SMC时，生长被完全抑制。细胞活力>95%，证实DETA/NO无细胞毒性。结果表明，NO供体可能是血管损伤（如球囊血管成形术）后内膜增生和再狭窄的有效抑制剂。
