Charbit M, Blazy I, Gogusev J, Pouzet B, Brocart D, Sachs C, Déchaux M
Department of Physiology, CHU Necker-Enfants Malades, Paris, France.
Pediatr Nephrol. 1997 Oct;11(5):617-22. doi: 10.1007/s004670050349.
The present study was designed to investigate the effects of chronic administration of the arginine analogue L-Name (50 mg/kg body weight), the angiotensin converting enzyme inhibitor, perindopril (2 mg/kg body weight), and perindopril (2 mg/kg) plus L-Name (50 mg/kg) on blood pressure, plasma renin activity, plasma angiotensinogen, and hepatic angiotensinogen mRNA levels in young and adult rats. The drugs were given daily from birth to day 21 to puppies and for 15 days to adults. Analytical procedures were performed on day 21 for the puppies and at 10 weeks for the adults. In puppies, blood pressure did not change with L-Name, it decreased to 45% of control values (P < 0.001) with perindopril, and decreased to 77% of control values (P < 0.05) with perindopril plus L-Name. In adults, blood pressure increased to 129% of control values (P < 0.02) with L-Name, decreased to 80% of control values (P < 0.05) with perindopril, and did not change with perindopril plus L-Name. Compared with controls, plasma renin activity was unchanged in puppies and adults with L-Name, undetectable in puppies and slightly increased in adults with perindopril, undetectable in puppies and slightly decreased in adults with perindopril plus L-Name. With L-Name, angiotensinogen mRNA levels were unchanged in puppies and slightly increased in adults, while plasma angiotensinogen levels were decreased (P < 0.05) in puppies and increased (P < 0.01) in adults; with perindopril, angiotensinogen mRNA levels were unchanged in puppies and slightly decreased in adults, while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.05) in adults; with perindopril plus L-Name, angiotensinogen mRNA levels were unchanged in puppies while plasma angiotensinogen levels were undetectable in puppies and decreased (P < 0.01) in adults. This study suggests that during the early postnatal period (1) nitric oxide does not exert a basal vasodilator tone but contributes to the hypotensive state induced by perindopril, (2) angiotensin II is essential to maintain blood pressure, (3) and angiotensinogen mRNA levels are not influenced by nitric oxide or angiotensin II.
本研究旨在探讨长期给予精氨酸类似物L-精氨酸甲酯(L-Name,50毫克/千克体重)、血管紧张素转换酶抑制剂培哚普利(2毫克/千克体重)以及培哚普利(2毫克/千克)加L-精氨酸甲酯(50毫克/千克)对幼龄和成年大鼠血压、血浆肾素活性、血浆血管紧张素原及肝脏血管紧张素原mRNA水平的影响。药物从出生后每日给予幼犬直至第21天,给予成年大鼠15天。在第21天对幼犬进行分析检测,成年大鼠在10周时进行检测。在幼犬中,L-精氨酸甲酯对血压无影响,培哚普利可使血压降至对照值的45%(P<0.001),培哚普利加L-精氨酸甲酯可使血压降至对照值的77%(P<0.05)。在成年大鼠中,L-精氨酸甲酯使血压升至对照值的129%(P<0.02),培哚普利使血压降至对照值的80%(P<0.05),培哚普利加L-精氨酸甲酯对血压无影响。与对照组相比,L-精氨酸甲酯对幼犬和成年大鼠的血浆肾素活性均无影响;培哚普利使幼犬血浆肾素活性无法检测到,成年大鼠略有升高;培哚普利加L-精氨酸甲酯使幼犬血浆肾素活性无法检测到,成年大鼠略有降低。使用L-精氨酸甲酯时,幼犬血管紧张素原mRNA水平无变化,成年大鼠略有升高,而幼犬血浆血管紧张素原水平降低(P<0.05),成年大鼠升高(P<0.0