Ito M, Oguri M, Naruse A, Ito H, Suzuki Y, Satake N, Shibata S
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
J Pharmacol Exp Ther. 1991 Jul 1;258(1):388-95.
A single i.v. injection of daunomycin (10 mg/kg) into rats produced severe proteinuria and hypercholesterolemia without atherosclerosis on the 20th and 40th days after the treatment. However, these changes were not observed on the 5th day. No change in systolic blood pressure was seen through the 40-day experimental period. Relaxation to acetylcholine, A23187 and nitroprusside was examined in aortic rings precontracted with phenylephrine (3 x 10(-6) M). Acetylcholine-induced relaxation was significantly attenuated in the nephrotic rats on the 20th and 40th days, in comparison to the control animals. In aortic rings taken from control and nephrotic rats on the 40th day, removal of the endothelium or treatment with methylene blue (10(-5) M) completely abolished the relaxation induced by acetylcholine (10(-5) M). In addition, acetylcholine (10(-5) M) induced a transient increase in the aortic cyclic GMP and this increase was completely abolished by removal of the endothelium. In the preparations of nephrotic rats on the 20th and 40th days, the cyclic GMP levels stimulated by acetylcholine (10(-5) M) were decreased to about 50% in comparison to their respective control. A23187 also evoked diminished relaxation in nephrotic rats on the 20th and 40th days. However, on the 40th day after the treatment, the effects of nitroprusside in relaxing the aorta and in elevating the cyclic GMP level in the aorta were not altered by nephrosis. In addition, the nitroprusside-induced relaxation and cyclic GMP accumulation were not affected by removal of the endothelium. These results indicate that endothelium-dependent relaxation is attenuated with the development of nephrosis.
给大鼠单次静脉注射柔红霉素（10毫克/千克）后，在治疗后的第20天和第40天会出现严重蛋白尿和高胆固醇血症，但无动脉粥样硬化。然而，在第5天未观察到这些变化。在整个40天的实验期内，收缩压未见变化。用去氧肾上腺素（3×10⁻⁶ M）预收缩主动脉环后，检测其对乙酰胆碱、A23187和硝普钠的舒张反应。与对照动物相比，肾病大鼠在第20天和第40天，乙酰胆碱诱导的舒张明显减弱。在第40天取自对照和肾病大鼠的主动脉环中，去除内皮或用亚甲蓝（10⁻⁵ M）处理可完全消除乙酰胆碱（10⁻⁵ M）诱导的舒张。此外，乙酰胆碱（10⁻⁵ M）可诱导主动脉环中环状GMP短暂升高，去除内皮可完全消除这种升高。在第20天和第40天的肾病大鼠标本中，乙酰胆碱（10⁻⁵ M）刺激的环状GMP水平与各自对照相比降低至约50%。A23187在第20天和第40天也使肾病大鼠的舒张减弱。然而，在治疗后的第40天，肾病并未改变硝普钠舒张主动脉及升高主动脉环状GMP水平的作用。此外，硝普钠诱导的舒张和环状GMP积累不受去除内皮的影响。这些结果表明，随着肾病的发展，内皮依赖性舒张减弱。
