Bernátová I, Kopincová J, Púzserová A, Janega P, Babál P
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Physiol Res. 2007;56 Suppl 2:S17-S24. doi: 10.33549/physiolres.931393. Epub 2007 Sep 5.
N(G)-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112+/-3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickness/diameter ratio of the aorta and the femoral artery of L-NAME-treated rats. NO synthase activity (determined by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline) was not altered in the hypothalamus of L-NAME-treated rats. Interestingly, chronic low-dose L-NAME treatment significantly elevated NO synthase activity in the left ventricle and aorta, increased endothelium-dependent acetylcholine-induced vasorelaxation and reduced serotonin-induced vasoconstriction of the femoral artery. The data suggest that chronic low-dose L-NAME treatment can increase NO production and vasorelaxation in normotensive rats without negative structural changes in the cardiovascular system.
N（G）-硝基-L-精氨酸甲酯（L-NAME）是一种非特异性一氧化氮（NO）合酶抑制剂，常用于诱导NO缺乏型高血压。本研究的目的是探讨长期低剂量给予L-NAME对大鼠NO生成、血管功能以及心脏和选定动脉结构的影响。成年雄性Wistar大鼠饮用含约1.5 mg/kg/天L-NAME的水，持续8周。大鼠的基础血压（通过尾套法测定）为112±3 mmHg。与对照组相比，低剂量给予L-NAME在治疗的第三周和第六周时显著升高血压，分别约升高9%和12%。在此之后，L-NAME处理组大鼠的血压恢复到对照值。L-NAME对相对左心室质量、心脏纤维化和胶原蛋白III/胶原蛋白I比值没有影响。同样，L-NAME处理组大鼠的主动脉和股动脉的横截面积以及壁厚/直径比也没有改变。L-NAME处理组大鼠下丘脑的NO合酶活性（通过将[（3）H]-L-精氨酸转化为[（3）H]-L-瓜氨酸来测定）没有改变。有趣的是，长期低剂量L-NAME处理显著提高了左心室和主动脉中的NO合酶活性，增加了内皮依赖性乙酰胆碱诱导的血管舒张，并减少了血清素诱导的股动脉血管收缩。数据表明，长期低剂量L-NAME处理可增加正常血压大鼠的NO生成和血管舒张，而不会对心血管系统产生负面结构变化。
