Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat

Abstract

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls ( n = 12), (2) nondiabetic controls administered losartan (70–80mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan ( n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan ( n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 ± 0.21 g) than in the controls (1.37 ± 0.14 g; P < .05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 ± 0.22, 1.73 ± 0.13, and 1.51 ± 0.14 g, respectively; P < .05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 ± 436, 596 ± 323, 567 ± 349, and 159 ± 28 pg/mL; P < .001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 ± 12 vs 117 ± 16 nmol/mL/min; P < .05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor–blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.