Lefer A M, Ma X L
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107-6799.
Arterioscler Thromb. 1993 Jun;13(6):771-6. doi: 10.1161/01.atv.13.6.771.
Hypercholesterolemia, before atherosclerosis, is known to reduce agonist- (e.g., acetylcholine) mediated nitric oxide (NO) production within 2 weeks of a cholesterol-enriched diet. However, no data exist on the effect of hypercholesterolemia on the basal release of NO from blood vessels. We studied the basal release of NO in rabbit coronary arteries by addition of the NO synthase blocker NG-nitro-L-arginine-methyl ester (L-NAME). Basal release of NO was markedly attenuated 2 weeks after introduction of a 0.5% cholesterol addition to the diet. One week later, the adherence of neutrophils to the coronary endothelium was significantly enhanced (i.e., threefold; p < 0.01 different from control). The increased adhesiveness could be attributed to enhanced endothelial adhesion rather than to changes in the properties of the leukocytes. Both phenomena could be reversed by addition of L-arginine to isolated coronary arteries. Administration of 10 mg/day lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, markedly attenuated both the reduced basal NO production and the increased adhesiveness of the endothelium. These results support the concept that NO is an important protective agent produced by the endothelium to preserve the integrity of the endothelium and may protect it against atherogenesis.
在动脉粥样硬化形成之前，高胆固醇血症已知会在富含胆固醇饮食的2周内降低激动剂（如乙酰胆碱）介导的一氧化氮（NO）生成。然而，关于高胆固醇血症对血管NO基础释放的影响尚无数据。我们通过添加NO合酶阻滞剂NG-硝基-L-精氨酸甲酯（L-NAME）来研究兔冠状动脉中NO的基础释放。在饮食中添加0.5%胆固醇2周后，NO的基础释放明显减弱。1周后，中性粒细胞与冠状动脉内皮的黏附显著增强（即增加了3倍；与对照组相比p < 0.01）。黏附性增加可归因于内皮黏附增强，而非白细胞特性的改变。通过向离体冠状动脉中添加L-精氨酸，这两种现象均可逆转。给予10mg/天的洛伐他汀（一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）可显著减弱基础NO生成的减少以及内皮黏附性的增加。这些结果支持了这样一种观点，即NO是内皮产生的一种重要保护剂，可维持内皮的完整性，并可能保护其免受动脉粥样硬化的影响。
