Hyperinsulinemia increases blood pressure and pup weight in pregnant rats

Abstract

Hyperinsulinemia and insulin resistance have been associated with gestational hypertensive disorders. The aims of this study were to investigate whether chronic hyperinsulinemia during euglycemia causes changes in cardiovascular, metabolic and reproductive systems of pregnant rats. On gestational day (GD) 14, Sprague Dawley rats were assigned to normal pregnant (NP) group or to NP+Ins group, in which miniosmotic pump with insulin (1.5 mU/kg/min) was placed subcutaneously and 20% glucose was added in drinking water. On GD 19, MAP was recorded, rats were sacrificed, and blood, placentas and pups were collected. Body weight (BW) and caloric intake (CI) were measured on GD 16–18. Serum insulin concentration was elevated in NP+Ins compared with NP (15.61 ± 1.39 vs 10.56 ± 0.68 μU/mL, P<0.05). There were no differences in blood glucose levels between groups. MAP was higher in NP+Ins compared with NP (114 ± 2 vs 104 ± 4 mmHg, P<0.05). There were no differences in BW between groups. CI was lower in NP+Ins compared with NP (55.24 ± 1.32 vs 69.98 ± 1.35 kcal/day, P<0.05). Although number of viable pups per rat and placenta weight were similar between groups, pups from NP+Ins were heavier than from NP (2.41 ± 0.02 vs 2.32 ± 0.03g, P<0.05). Thus insulin appears to raise blood pressure, suppress appetite and increase pup weight in pregnancy, representing a possible mechanism to induce hypertension in gestational hypertensive disorders. Funded by NIH grants HL51971 and 1T32HL105324.