Hypertension and nephrotoxic lesions in rats 1 year after prenatal exposure to gentamicin

Abstract

Using the aminoglycoside antibiotic gentamicin persistant functional and morphological changes were induced prenatally in the rat kidney. After 6 days of s.c. treatment (110 mg gentamicin/kg body wt) from day 10 to 15 of pregnancy complete resorption was noticed in 8 of the 14 treated animals. Fifty-three newborn were obtained from six dams. One year later only 26 rats (16 male, 10 female) were still alive. The systolic arterial pressure of the female offspring was significantly increased (139±15 mm Hg versus 112±9 mmHg) compared with controls. No statistically significant effect could be noticed in the male offspring (128±5 mm Hg versus 118±21 mm Hg). Corresponding results were obtained from analysis of urea plasma concentrations. Another cohort of pregnant rats received daily injections of gentamicin from day 15 to 20 of pregnancy (110 mg/kg body wt s.c.). In this group 59 newborn from a total of 109 died within the first 5 days after birth. Six litters were observed postnatally. One year after birth the following blood pressure values were determined: 122±4 mm Hg (male) and 132±17 mm Hg (female). Urea plasma concentrations were significantly higher in female, but not in male, offspring. Light and electron microscopic inspection revealed pathological changes in the kidneys of the female offspring only. The degree of maternal kidney damage — which shows considerable variations — was monitored during the treatment period. For this purpose the plasma gentamicin and urea concentrations were measured on 3 days of treatment in all of the pregnant animals. The postnatal data (mortality, blood pressure, and urea plasma concentrations) show a correlation to the degree of maternal kidney impairment.