Medicolegal study on alcohol-induced sudden death.(Effect of ethanol on vascular responses)

内皮细胞不仅可以产生和/或释放内皮源性松弛因子（EDRF），即一氧化氮（NO），还可以产生和/或释放内皮超极化因子（EDHF），使平滑肌细胞超极化。EDRF激活鸟苷酸环化酶，增加平滑肌细胞环化GMP，导致平滑肌松弛。已知乙醇可抑制由EDRF介导的松弛反应。然而，关于乙醇是否可以抑制EDHF介导的松弛反应，目前还没有报道。因此，我们利用离体大鼠肠系膜上动脉研究了乙醇对edhf介导的松弛反应的影响。乙酰胆碱在内皮存在时产生松弛反应。NO抑制剂N^ g -硝基- l -精氨酸（L-NNA）可部分抑制松弛反应。20 mM KCl和Ca^<++>活化的K通道抑制剂（四乙基铵和4氨基吡啶）可消除L-NNA耐药松弛，但对atp敏感的K通道抑制剂格列本脲不起作用。因此，耐药弛豫被认为是由EDHF介导的，EDHF打开了ca激活的K通道。EtOH对l - na抗性弛豫也有抑制作用，但对硝普钠诱导的弛豫无抑制作用。这些结果表明，乙醇可以抑制EDHF和EDRF诱导的松弛，其抑制机制不是对平滑肌细胞的非特异性作用。虽然乙醇对edhf介导的松弛的抑制机制可能被认为发生在内皮细胞水平，但需要进一步的研究来阐明其机制。

Endothelial cells can produce and/or release not only endothelium-dereved relaxing factor (EDRF), identified as nitric oxide (NO), but also endothelium-hyperpolarizing factor (EDHF) which can hyperpolarize smooth muscle cells. EDRF activates guanylate cyclase and increases GMP in cyclic in smooth muscle cells, leading to relaxation of smooth muscles.Ethanol is known to depress the relaxation response mediated by EDRF.However, there is no report as to whether ethanol can depress the relaxation response mediated by EDHF,which is not identified as yet. Therefore, we investigated the effect of ethanol on EDHF-mediated relaxation response using isolated rat superior mesenteric artery. Acetylcholine produced relaxation response in the presence of endothelium. The relaxation responses were partially depressed by NO inhibitor, N^G-nitro-L-arginine (L-NNA). The L-NNA resistant relaxations were abolished by 20 mM KCl and Ca^<++>-activated K channel inhibitors, tetraethylammonium and 4 aminopyridine but not ATP-sensitive K channel inhibitor, glibenclamide. Thus, the resistant relaxations were considered to be mediated by EDHF,which opens Ca-activated K channels. EtOH also depressed the L-NNA-resistant relaxations but not the relaxations induced by sodium nitroprusside. These results suggest that ethanol can depress the relaxations induced by both EDHF and EDRF and that the inhibitory mechanism is not non-specific action on smooth muscle cells. Although the inhibitory mechanisms of ethanol on EDHF-mediated relaxations is probably considered to occur at the level of endothelial cells further study is required to clarify the mechanisms.