Dworkin L D, Tolbert E, Recht P A, Hersch J C, Feiner H, Levin R I
Department of Medicine, Brown University, Rhode Island Hospital, Providence 02903, USA.
Hypertension. 1996 Feb;27(2):245-50. doi: 10.1161/01.hyp.27.2.245.
The objective of this study was to determine whether the calcium antagonist amlodipine could slow the progression of chronic renal disease. We examined the effects of amlodipine on kidney structure and function in two experimental models of hypertension. In the first study, adult, male Munich Wistar rats underwent uninephrectomy and were given weekly injections of desoxycorticosterone and 1% saline for drinking. Rats ingested normal chow or chow containing amlodipine for 8 weeks. The drug reduced systemic blood pressure, but glomerular filtration rate, kidney weight, proteinuria, and morphological evidence of glomerular injury were not affected. In the second study, male spontaneously hypertensive rats underwent uninephrectomy at 5 weeks of age and were followed for 6 months, during which they received no therapy or amlodipine. The drug dose was determined in preliminary studies to be the highest dose not associated with marked growth retardation. Again, although systemic blood pressure was significantly reduced by amlodipine, proteinuria and the prevalence of glomerulosclerosis were similar in amlodipine-treated and control spontaneously hypertensive rats. Micropuncture studies revealed that glomerular pressure remained elevated in amlodipine-treated spontaneously hypertensive rats. Kidney weight and glomerular volume were also similar in amlodipine-treated and control rats. Amlodipine also failed to inhibit platelet aggregation. Therefore, antihypertensive therapy with amlodipine fails to reduce glomerular pressure in spontaneously hypertensive rats as well as glomerular size and injury in spontaneously hypertension rats and desoxycorticosterone-salt hypertension. Although other dihydropyridine calcium antagonists have been found to reduce experimental glomerular injury, these data suggest that amlodipine may not prevent hypertensive nephrosclerosis.
本研究的目的是确定钙拮抗剂氨氯地平是否能减缓慢性肾病的进展。我们在两种高血压实验模型中研究了氨氯地平对肾脏结构和功能的影响。在第一项研究中，成年雄性慕尼黑Wistar大鼠接受单侧肾切除术，并每周注射脱氧皮质酮，饮用1%盐水。大鼠摄入普通饲料或含氨氯地平的饲料8周。该药物降低了全身血压，但肾小球滤过率、肾脏重量、蛋白尿以及肾小球损伤的形态学证据均未受到影响。在第二项研究中，雄性自发性高血压大鼠在5周龄时接受单侧肾切除术，并随访6个月，在此期间它们未接受任何治疗或给予氨氯地平。在初步研究中确定该药物剂量为与明显生长迟缓无关的最高剂量。同样，尽管氨氯地平显著降低了全身血压，但氨氯地平治疗组和对照组自发性高血压大鼠的蛋白尿和肾小球硬化患病率相似。微穿刺研究显示，氨氯地平治疗的自发性高血压大鼠肾小球压力仍升高。氨氯地平治疗组和对照组大鼠的肾脏重量和肾小球体积也相似。氨氯地平也未能抑制血小板聚集。因此，氨氯地平抗高血压治疗未能降低自发性高血压大鼠的肾小球压力，以及自发性高血压大鼠和脱氧皮质酮-盐性高血压大鼠的肾小球大小和损伤。尽管已发现其他二氢吡啶类钙拮抗剂可减轻实验性肾小球损伤，但这些数据表明氨氯地平可能无法预防高血压性肾硬化。
