Paller M S
Department of Medicine, University of Minnesota, Minneapolis 55455.
Transplantation. 1988 Jun;45(6):1126-31. doi: 10.1097/00007890-198806000-00026.
Acute infusion of cyclosporine in rats causes intense renal vasoconstriction and decreased glomerular filtration rate, effects that persist during short-term daily administration. We tested whether the orally active prostaglandin E1 analog misoprostol could reverse cyclosporine-induced renal vasoconstriction and restore the glomerular filtration rate. Male Sprague-Dawley rats were infused with cyclosporine (10 mg/kg) and then given an oral dose of misoprostol (100, 500, or 1000 micrograms/kg). Cyclosporine caused large decreases in glomerular filtration rate and renal blood flow and a large increase in renal vascular resistance. Misoprostol decreased renal vascular resistance and increased renal blood flow and glomerular filtration rate to near normal levels. The two highest doses of misoprostol caused severe hypotension only in cyclosporine-treated animals. However, when it was given in a dose of 100 micrograms/kg hypotension was not a serious problem. This dose of misoprostol resulted in an increase in glomerular filtration rate from 341 +/- 57 to 669 +/- 104 microliter/min (P less than 0.005) and renal blood flow from 2.23 +/- 0.36 to 4.25 +/- 0.65 ml/min (P less than 0.01), as well as a decrease in renal vascular resistance from 73.7 +/- 23.8 to 29.4 +/- 5.8 mmHg/ml/min (P less than 0.05) in cyclosporine-treated animals. When given to control animals, misoprostol had no effects on renal hemodynamics or renal function. In summary, acute cyclosporine-induced renal vasoconstriction and renal dysfunction in the rat were substantially reversed by oral administration of the prostaglandin E1 analog misoprostol.
给大鼠急性输注环孢素会导致强烈的肾血管收缩和肾小球滤过率降低，这些效应在短期每日给药期间持续存在。我们测试了口服活性前列腺素E1类似物米索前列醇是否能逆转环孢素诱导的肾血管收缩并恢复肾小球滤过率。雄性Sprague-Dawley大鼠先输注环孢素（10毫克/千克），然后口服一剂米索前列醇（100、500或1000微克/千克）。环孢素导致肾小球滤过率和肾血流量大幅下降，肾血管阻力大幅增加。米索前列醇降低了肾血管阻力，增加了肾血流量和肾小球滤过率，使其接近正常水平。米索前列醇的两个最高剂量仅在环孢素治疗的动物中引起严重低血压。然而，当以100微克/千克的剂量给药时，低血压不是一个严重问题。这个剂量的米索前列醇使环孢素治疗的动物的肾小球滤过率从341±57增加到669±104微升/分钟（P<0.005），肾血流量从2.23±0.36增加到4.25±0.65毫升/分钟（P<0.01），肾血管阻力从73.7±23.8降低到29.4±5.8毫米汞柱/毫升/分钟（P<0.05）。当给予对照动物时，米索前列醇对肾血流动力学或肾功能没有影响。总之，口服前列腺素E1类似物米索前列醇可显著逆转大鼠急性环孢素诱导的肾血管收缩和肾功能障碍。
