Cardiovascular and renal characteristics, and responses to acute volume expansion of a rat model of diabetic pregnancy

The objective of this study was to characterize the cardiovascular and renal alterations that occur during diabetic pregnancy, and to evaluate the effect of insulin treatment in 12-14 days pregnant diabetic rats. Four groups of female Sprague Dawley rats were studied: virgin control group (NP), pregnant control group (CP), diabetic pregnant group (DP), and diabetic pregnant group with insulin treatment (DPI). Systolic arterial pressure (SAP) was increased on day 12, whereas heart rate (HR) decreased starting with day 3 in DP group of rats. DP rats exhibited marked renal hypertrophy with greater kidney weight (wt) and kidney wt/body wt ratio. Insulin treatment normalized blood glucose (BG) concentration, SAP and HR, and prevented the increase in kidney wt/body wt ratio in DPI rats. At the time of the terminal acute experiment, acute saline volume expansion (VE, 5% body wt/30 min) significantly increased renal interstitial hydrostatic pressure (RIHP), urinary sodium excretion (U _NaV) and urine flow rate (V) in all groups, but the increases (Δ) were significantly attenuated in both CP (1.7 ± 0.2mmHg, 12.0 ± 1.5 μEq.min^-1.g kidney wt^-1 and 76.2 ± 10.9 μl.min^-1.g kidney wt^-1 for ΔRIHP, ΔU_NaV and ΔV respectively) and DP (1.3 ± 0.1 mmHg, 6.8 ± 1.8 μEq.min^-1.g kidney wt^-1 and 32.3 ± 9.3 μl.min^-1.g kidney wt^-1 for ΔRIHP, ΔU_NaV and ΔV respectively) group of rats as compared to NP (4.0 ± 0.6 mmHg, 21.6 ± 1.4 μEq.min^-1.g kidney wt^-1and 136.8 ± 10.5 μl.min^-1.g kidney wt ^-1 for ΔRIHP, ΔU_NaV and ΔV respectively) group of rats. Although RIHP response to VE was similar in DP and CP group of rats, the natriuretic and diuretic responses to VE were significantly lower in DP as compared to CP group of rats. Insulin treatment had no effect on RIHP response (ΔRIHP = 1.5 ± 0.3 mmHg), but restored most of the natriuretic (ΔU_NaV = 15.7 ± 2.9 μEq.min ^-1.g kidney wt^-1) and diuretic (ΔV = 100.2 ± 19.3 μl.min^-1.g kidney wt^-1) responses to VE in DPI as compared with CP group of rats. These data suggest that with VE, the restoration of the increase in U_NaV and V with insulin treatment in diabetic pregnant rats is not mediated by changes in RIHP.