Campos S B, Seguro A C, Cesar K R, Rocha A S
Laboratório de Pesquisa Básica, Nefrologia Faculdade de Medicina, Universidade de São Paulo, Brasil.
Nephron. 1992;62(1):74-9. doi: 10.1159/000186999.
The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.
研究了阿昔洛韦（腹腔注射100mg/kg体重，持续7天）对大鼠的肾脏影响。所有动物均出现多尿，血尿素氮、钠和钾的排泄分数增加。在输注低渗盐水期间，与正常大鼠相比，阿昔洛韦处理的大鼠远端排泄分数更高（27.8±4.7对11.3±0.9%，p<0.01），自由水清除率与远端钠排泄的比值更低（33.5±7.8对57.2±3.9%，p<0.02）。在输注高渗盐水后，阿昔洛韦处理的大鼠渗透压清除率与菊粉清除率的比值高于正常大鼠（47.8±7.4%对27.0±4.8%），而阿昔洛韦处理的大鼠自由水重吸收与渗透压清除率的比值更低（13.6±4.6对38.2±3.2%，p<0.01）。这些发现提示阿昔洛韦对近端小管、髓袢升支粗段和/或内髓集合管（IMCD）有影响。对正常大鼠灌注IMCD的3H2O通透性进行体外测量显示，向浴槽中添加血管加压素（50μU/ml）可增加扩散水通透性（43.4±4.8对105.6±9.1×10−5cm/s），而在阿昔洛韦处理的大鼠中，在血管加压素存在的情况下，对照值（58.8±9.1×10−5cm/s）没有显著增加（71.3±13.6×10−5cm/s）。这些结果表明，高剂量阿昔洛韦会导致氮质血症以及近端小管和髓袢升支粗段功能异常，并伴有IMCD对血管加压素的抵抗。
