PMID- 23955606 OWN - NLM STAT- MEDLINE DCOM- 20140304 LR - 20211021 IS - 1941-7225 (Electronic) IS - 0895-7061 (Print) IS - 0895-7061 (Linking) VI - 26 IP - 12 DP - 2013 Dec TI - Euglycemic hyperinsulinemia increases blood pressure in pregnant rats independent of placental antiangiogenic and inflammatory factors. PG - 1445-51 LID - 10.1093/ajh/hpt137 [doi] AB - BACKGROUND: Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor alpha (TNF- alpha) levels and hypertension in pregnant rats. METHODS: On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to placental sFlt-1 and TNF-alpha levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured. RESULTS: MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-alpha concentrations between groups. CONCLUSIONS: In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia. FAU - Palei, Ana C AU - Palei AC AD - Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi. FAU - Spradley, Frank T AU - Spradley FT FAU - Granger, Joey P AU - Granger JP LA - eng GR - P01 HL051971/HL/NHLBI NIH HHS/United States GR - T32 HL105324/HL/NHLBI NIH HHS/United States GR - 1T32HL105324/HL/NHLBI NIH HHS/United States GR - HL051971/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130816 PL - United States TA - Am J Hypertens JT - American journal of hypertension JID - 8803676 RN - 0 (Biomarkers) RN - 0 (Insulin) RN - 0 (Leptin) RN - 0 (Triglycerides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Biomarkers/*blood MH - Blood Pressure/*drug effects MH - Cholesterol/blood MH - Disease Models, Animal MH - Female MH - Glucose/metabolism MH - Heart Rate/drug effects MH - Hyperinsulinism/*blood MH - Hypertension/*blood MH - Insulin/blood MH - Leptin/blood MH - Placenta/*physiopathology MH - Pre-Eclampsia/blood/physiopathology MH - Pregnancy MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Triglycerides/blood MH - Tumor Necrosis Factor-alpha/blood MH - Vascular Endothelial Growth Factor Receptor-1/blood PMC - PMC3816628 OTO - NOTNLM OT - blood pressure OT - hyperinsulinemia OT - hypertension OT - preeclampsia. OT - pregnancy EDAT- 2013/08/21 06:00 MHDA- 2014/03/05 06:00 PMCR- 2014/12/01 CRDT- 2013/08/20 06:00 PHST- 2013/08/20 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2014/03/05 06:00 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - hpt137 [pii] AID - 10.1093/ajh/hpt137 [doi] PST - ppublish SO - Am J Hypertens. 2013 Dec;26(12):1445-51. doi: 10.1093/ajh/hpt137. Epub 2013 Aug 16.