EFFECT OF CYCLOSPORINE ADMINISTRATION ON RENAL HEMODYNAMICS IN CONSCIOUS RATS
EFFECT OF CYCLOSPORINE ADMINISTRATION ON RENAL HEMODYNAMICS IN CONSCIOUS RATS
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DOI：
10.1038/ki.1985.196
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发表时间：
1985-11-01
影响因子：
19.6
通讯作者：
FERRIS, TF
中科院分区：
文献类型：
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作者：
MURRAY, BM;PALLER, MS;FERRIS, TF
在清醒的大鼠中研究了急性和慢性给予环孢菌素对全身和肾脏血流动力学的影响。以20 mg/kg（Cy 20）剂量输注环孢菌素导致肾血流量（RBF）显着下降（3.4 vs. 6.5 ml/min/g，P < 0.05），肾血管阻力（RVR）升高（36.9 vs. 20.6 mm Hg/ml/min/g，P < 0.05）。以 10 mg/kg (Cy 10) 剂量输注环孢菌素不会导致 RBF 或 RVR 发生显着变化。两种剂量的环孢菌素均导致血浆肾素活性(PRA)从对照值5.6.+-受到刺激。每小时 0.8 ng/ml 至 11.6 .+-。 2.0，10 mg/kg 和 26.7 .+-。 5.6 20 毫克/千克。尿 6-酮-PFG1.alpha。排泄量较对照值 14.0.+- 有所增加。 2.0 纳克/6 小时至 22.7 .+-。 2.2 10 mg/kg 和 25.0 .+-。 2.0，20 毫克/千克。对 RBF、RVR、PRA 和 6-keto-PGF1.alpha 具有类似的作用。长期给予环孢素（20mg/kg，腹腔注射7天）后观察到排泄。用卡托普利预处理动物并不能阻止环孢素后 RBF 的下降，表明血管收缩不是由血管紧张素 II 介导的。用甲氯芬那酯治疗的动物显示，10 mg/kg 环孢素可降低 RBF（4.3 vs. 7.0 ml/min/g，P < 0.05），表明前列腺素可防止环孢素的血管收缩作用。环孢菌素后给予苯氧苯扎明可改善 RBF（5.0 与 3.4 ml/min/g）并使 RVR 恢复正常。同样，去肾神经可以显着降低环孢素治疗后 RBF 的下降（神经支配的右肾 3.6 对比去神经左肾 6.0 ml/min/g，P < 0.001）。我们得出的结论是，环孢菌素引起肾血管收缩，这是由肾交感神经系统介导的，并且使用环加氧酶抑制剂会加剧血管收缩。
The effect of acute and chronic administration of cyclosporine on systemic and renal hemodynamics was studied in conscious rats. Infusion of cyclosporine in a dose of 20 mg/kg (Cy 20) resulted in a significant fall in renal blood flow (RBF) (3.4 vs. 6.5 ml/min per g, P < 0.05) and a rise in renal vascular resistance (RVR) (36.9 vs. 20.6 mm Hg/ml per min per g, P < 0.05). Infusion of cyclosporine at a dose of 10 mg/kg (Cy 10) did not result in a significant change in RBF or RVR. Both doses of cyclosporine resulted in stimulation of plasma renin activity (PRA) from control values of 5.6 .+-. 0.8 ng/ml per hr to 11.6 .+-. 2.0 with 10 mg/kg and 26.7 .+-. 5.6 with 20 mg/kg. Urinary 6-keto-PFG1.alpha. excretion increased from control values of 14.0 .+-. 2.0 ng/6hr to 22.7 .+-. 2.2 with 10 mg/kg and 25.0 .+-. 2.0 with 20 mg/kg. Similar effects on RBF, RVR, PRA, and 6-keto-PGF1.alpha. excretion were seen after chronic administration of cyclosporine (20 mg/kg i.p. for 7 days). Pretreatment of animals with captopril did not prevent the fall in RBF after cyclosporine, suggesting that the vasoconstriction was not mediated by angiotensin II. Animals treated with meclofenamate demonstrated reduction of RBF with 10 mg/kg cyclosporine (4.3 vs. 7.0 ml/min per g, P < 0.05), suggesting that prostaglandins protect against the vasoconstrictor effect of cyclosporine. Administration of pheoxybenzamine after cyclosporine improved RBF (5.0 vs. 3.4 ml/min per g) and restored RVR to normal. Similarly, renal denervation dramatically reduced the fall in RBF after cyclosporine (innervated right kidney 3.6 vs. denervated left kidney 6.0 ml/min per g, P < 0.001). We conclude that cyclosporine causes renal vasoconstriction, which is mediated by the renal sympathetic nervous system, and that vasoconstriction is exacerbated by the administration of cyclooxygenase inhibitors.