INHIBITION OF RAT MESANGIAL CELL MITOGENESIS BY NITRIC OXIDE-GENERATING VASODILATORS
INHIBITION OF RAT MESANGIAL CELL MITOGENESIS BY NITRIC OXIDE-GENERATING VASODILATORS
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DOI：
10.1152/ajprenal.1989.257.1.f60
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发表时间：
1989-07-01
影响因子：
--
通讯作者：
HASSID, A
中科院分区：
文献类型：
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作者：
GARG, UC;HASSID, A
最近的研究表明，内皮源性舒张因子（EDRF）可能与一氧化氮（NO）相同。本研究旨在探讨一氧化氮生成药物对体外培养的系膜细胞的抗有丝分裂作用。产生NO的S-亚硝基-N-乙酰青霉胺、硝普钠和硝酸异山梨酯剂量依赖性地抑制血清刺激的DNA合成。所有这三种药物也抑制细胞增殖的速度，而硝普钠和S-亚硝基-N-乙酰青霉胺减少细胞密度在融合。S-亚硝基-N-乙酰青霉胺的抗有丝分裂活性在培养基中是不稳定的，可以被血红蛋白抑制，支持这样的观点，即NO，在游离或结合形式，是最终的效应。所有三种血管扩张剂均剂量依赖性地增加细胞鸟苷3“，5”-环一磷酸（cGMP）水平;此外，8-溴-cGMP模拟NO生成药物的作用，表明cGMP可能是抗有丝分裂的细胞内介质。S-亚硝基-N-乙酰青霉胺的生长抑制作用是可逆的，并不是由于细胞毒性所示的细胞活力的几个标准。这些结果提高了EDRF/NO可能是体内系膜细胞生长的调节剂的可能性。
Recent studies indicate that endothelium-derived relaxing factor (EDRF) may be identical with nitric oxide (NO). The purpose of this study was to investigate the antimitogenic effect of NO-generating drugs in cultured mesangial cells. S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and isosorbide dinitrate, which generate NO, dose dependently inhibited serum-stimulated DNA synthesis. All three drugs also inhibited the rate of cell proliferation, whereas sodium nitroprusside and S-nitroso-N-acetylpenicillamine decreased cell density at confluence. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was labile in culture medium and could be inhibited by hemoglobin, supporting the view that NO, in free or bound form, was the ultimate effector. All three vasodilators increased cellular guanosine 3'',5''-cyclic monophosphate (cGMP) levels dose dependently; moreover, 8-bromo-cGMP mimicked the effects of the NO-generating drugs, suggesting that cGMP may be an intracellular mediator of antimitogenesis. The growth-inhibitory effect of S-nitroso-N-acetylpenicillamine was reversible and was not due to cell toxicity as shown by several criteria of cell viability. The results raise the possibility that EDRF/NO may be a modulator of mesangial cell growth in vivo.