Function of vascular endothelium and vasomotor nerve in atherosclerotic animals

为了检测动脉粥样硬化和高脂血症对血管功能的影响，首先检测了正常动物的内皮功能（1，2）。然后，在Watanabe遗传性高脂血症（WHHL）家兔（3）和高胆固醇饮食喂养的高脂血症猴（4）中检查动脉粥样硬化和高脂血症对内皮和血管神经功能的影响。在离体猴舌动脉中，乙酰胆碱诱导的舒张作用是由内皮细胞色素P450 3A4亚型产生的花生四烯酸介导的一氧化氮（NO）和Ca^2+依赖性K^+通道开放底物介导的.在离体犬阴茎海绵体，乙酰胆碱引起的舒张作用是由NO和开放Ca^2+依赖性小电导K^+通道的物质介导的.在所有WHHL家兔颈动脉中均观察到明显的斑片状动脉粥样硬化病变。乙酰胆碱引起的内皮依赖性舒张反应被显著抑制 ...更多信息 在WHHL兔颈动脉粥样硬化病变。在WHHL兔的动脉粥样硬化和非动脉粥样硬化中，P物质的抑制性、内皮依赖性舒张作用均大于日本白色兔的动脉。因此，动脉粥样硬化可能抑制毒蕈碱受体功能。长期暴露于高脂血症可能导致内皮细胞P物质受体超敏反应。动脉粥样硬化病变没有观察到大脑中动脉（MCA）分离高脂血症猴喂养的高胆固醇饮食。与对照组猴的动脉相比，高血压猴MCA中由内皮NO介导的组胺诱导的舒张作用显著增强，而Ca^2+离子载体A23187的舒张作用在对照组和高血压猴之间没有差异。高脂血症不影响尼古丁引起的MCA舒张作用，这种舒张作用是由一氧化氮能神经释放的NO介导的。因此，高脂血症不影响猴MCA的内皮和一氧化氮能神经功能，但增强了组胺引起的NO介导的舒张作用，这可能是由于组胺受体介导的内皮功能上调。但一般不影响内皮和支配神经的功能。少

In order to examine the effects of atherosclerosis and hyperlipidemia on vascular function, endothelial function in normal animals was firstly examined (1, 2). Then, the effects of atherosclerosis and hyperlipidemia on the functions of endothelium and vasomotor nerves were examined in Watanabe heritable hyperlipidemic (WHHL) rabbits (3) and hyperlipidemic monkeys fed by a high cholesterol diet (4).1. In isolated monkey lingual arteries, acetylcholine-induced relaxation was mediated by nitric oxide (NO) and Ca^<2+>-dependent K^<+>-channel opening substarice(s) from arachidonic acid produced by cytochrome P450 3A4 isoform in the endothelium.2. In isolated dog corpus cavernosum, acetylcholine-induced relaxation was mediated by NO and substance(s) which opens Ca^<2+>-dependent K^<+>-channel of small conductance.3. Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit carotid arteries. Endothelium-dependent relaxations induced by acetylcholine were significantly inhibited … More in the WHHL rabbit carotid arteries with atherosclerotic lesions. Inversely, endothelium-dependent relaxations by substance P were greater in the arteries with and without atherosclerosis from WHHL rabbits than those in the arteries from Japanese white rabbits. Therefore, atherosclerosis may inhibit the muscarinic receptor function. Long exposure to hyperlipidemia was expected to cause receptor-hypersensitivity of substance P in the endothelium.4. Atherosclerotic lesions were not observed in middle cerebral arteries (MCA) isolated from hyperlipidemic monkeys fed by a high cholesterol diet. Histamine-induced relaxation, which was mediated by endothelial NO, was significantly potentiated in the hyperlipidemic monkey MCA, compared to that in the arteries from control monkeys whereas the relaxation by Ca^<2+> ionophore A23187 did not differ between control and hyperlipidemic monkeys. Nicotine- induced relaxation in MCA, which was mediated by NO released from nitroxidergic (nitrergic) nerves, was not affected by hyperlipidemia. Therefore, hyperlipidemia did not affect endothelial and nitroxidergic nerve functions of monkey MCA, but enhanced NO-mediated relaxation caused by histamine, possibly due to upregulation of histamine receptor-mediated function in the endothelium.From the findings using hyperlipidemic rabbits and monkeys, atherosclerosis and hyperlipidemia may modify the specific receptor functions in the endothelium, but not generally affect the functions of endothelium and innervating nerves. Less