Gentamicin-induced glomerulotoxicity in the pregnant rat

Ten daily injections of gentamicin, 40 mg/kg/d intraperitoneal (IP), produced a marked reduction in the glomerular capillary ultrafiltration coefficient (Kf) of virgin female Munich-Wistar rats without eliciting significant reductions in glomerular filtration rate (GFR) or single nephron (SN)GFR. A similar gentamicin-induced decrease in Kf was seen in midterm pregnant (day 12) rats and the normal gestational increase in GFR and SNGFR was blunted by gentamicin. Concomitant converting enzyme inhibition (CEI) (MK 421, 50 mg/L drinking water) completely prevented the gentamicin-induced decrease in Kf in virgin females, thus confirming that the gentamicin-induced decline in Kf is mediated by angiotensin II (ANG II). These studies indicate that pregnancy neither exacerbates nor ameliorates gentamicin-induced glomerulotoxicity and also that glomerular ANG II responsivity is not diminished in midterm pregnant rats.