Institute of Normal and Pathological Physiology, Centre of Excellence for Examination of Regulatory Role of Nitric Oxide in Civilisation Diseases, Slovak Academy of Sciences, Bratislava, Slovak Republic.
J Physiol Pharmacol. 2013 Feb;64(1):35-9.
The aim of this study was to investigate the long-term effects of 7-nitroindazole on the heart, kidneys, thoracic aorta, and carotid arteries from the progeny of mothers that had been treated with 7-nitroindazole (7NI) (10 mg/kg/day in drinking water) during gestation and nursing. The offspring were also treated with 7NI (10 mg/kg/day in drinking water) until 10 weeks of age. Mean arterial pressure (BP) was measured by tail-cuff plethysmography starting at 4 weeks of age. After perfusion fixation with glutaraldehyde at 120 mmHg, the heart and kidneys were weighed and the thoracic aorta and carotid arteries were processed for morphological investigation. The BP and body weight of treated rats did not differ from age-matched control rats during the course of the experiment. In the experimental group, at the end of the experiment, the heart weight/body weight and kidney weight/body weight ratios were decreased. In addition, the wall thickness (intima + media), cross sectional area (intima + media), and wall thickness/inner diameter ratio were significantly decreased in both the thoracic aorta and carotid arteries without a change in the inner vessel diameter. Circumferential wall tension was increased in both arteries. The data clearly indicate that long-term inhibition of neuronal nitric oxide (NO) synthase with the specific inhibitor 7NI evokes BP-independent hypotrophy of the heart, kidneys, and conduit arterial walls in normotensive Wistar rats.
本研究旨在探讨母体在妊娠和哺乳期接受 7-硝基吲唑(7NI)(10mg/kg/天饮水)治疗后,其后代的心脏、肾脏、胸主动脉和颈动脉的长期影响。后代也接受 7NI(10mg/kg/天饮水)治疗至 10 周龄。从 4 周龄开始,通过尾套容积描记法测量平均动脉压(BP)。在 120mmHg 的戊二醛灌注固定后,测量心脏和肾脏的重量,并对胸主动脉和颈动脉进行形态学研究。在实验过程中,接受治疗的大鼠的 BP 和体重与同龄对照组大鼠没有差异。在实验组,实验结束时,心脏重量/体重和肾脏重量/体重比值降低。此外,胸主动脉和颈动脉的壁厚度(内膜+中膜)、横截面积(内膜+中膜)和壁厚度/内径比值显著降低,而内血管直径没有变化。在两条动脉中,周向壁张力增加。这些数据清楚地表明,使用特定的神经元型一氧化氮合酶抑制剂 7NI 长期抑制,可引起正常血压的 Wistar 大鼠心脏、肾脏和导血管壁的 BP 非依赖性萎缩。