Sabra R, Takahashi K, Branch R A, Badr K F
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Pharmacol Exp Ther. 1990 Apr;253(1):34-7.
Amphotericin B infusions cause acute reductions in renal plasma flow and glomerular filtration rate. The exact mechanism by which these changes occur has not been identified fully, nor have the effects of the drug on the renal microcirculation been studied adequately. In this study, we examined the effect of intrarenal amphotericin B infusions (0.05 mg/kg/min) on glomerular hemodynamics in the anesthetized rat. Amphotericin B did not affect systemic blood pressure and slightly increased hematocrit (5%), but significantly decreased renal blood flow and glomerular filtration rate by 40 and 35%, respectively. Glomerular micropuncture revealed decreases in single nephron plasma flow and glomerular filtration rate (from 142 +/- 12 to 89 +/- 14 and from 35.3 +/- 2.2 to 22.8 +/- 2.8 nl/min, respectively). These changes were due to significant increases in pre- and postglomerular resistances (from 1.91 +/- 0.17 to 3.95 +/- 0.38 and from 1.30 +/- 0.10 to 2.08 +/- 0.12 10(10) dyn.sec.cm-5, respectively), and to a significant decrease in the glomerular capillary ultrafiltration coefficient which fell from 0.043 +/- 0.008 to 0.032 +/- 0.009 nl/(sec.mm Hg). These results provide further insight into the mechanisms of the acute renal effects of amphotericin B, and suggest possible mediators that may be involved in these effects.
两性霉素B输注会导致肾血浆流量和肾小球滤过率急性降低。这些变化发生的确切机制尚未完全明确,而且该药物对肾微循环的影响也未得到充分研究。在本研究中,我们检测了肾内输注两性霉素B(0.05mg/kg/min)对麻醉大鼠肾小球血流动力学的影响。两性霉素B不影响全身血压,使血细胞比容略有升高(5%),但显著降低肾血流量和肾小球滤过率,分别降低了40%和35%。肾小球微穿刺显示单个肾单位血浆流量和肾小球滤过率降低(分别从142±12降至89±14以及从35.3±2.2降至22.8±2.8nl/min)。这些变化是由于肾小球前和肾小球后阻力显著增加(分别从1.91±0.17增至3.95±0.38以及从1.30±0.10增至2.08±0.12×10¹⁰dyn·sec·cm⁻⁵),以及肾小球毛细血管超滤系数显著降低,从0.043±0.008降至0.032±0.009nl/(sec·mmHg)。这些结果为两性霉素B急性肾效应的机制提供了进一步的见解,并提示了可能参与这些效应的介质。