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Prenatal origins of hypertension induced by gestational undernutrition or environmental chemical exposure
ELLIS-HUTCHINGS, R. G., R. M. ZUCKER, C. LAU, B. E. GREY, AND J. M. ROGERS. Prenatal origins of hypertension induced by gestational undernutrition or environmental chemical exposure. Presented at Teratology Society Annual Meeting, Monterey, CA, June 28 - July 03, 2008.
Presentation @ Teratology 2008
Epidemiological studies have shown that babies of low birth weight have high blood pressure (BP) as children and adults, suggesting prenatal cardiovascular programming. This programming has been attributed to factors including undernutrition and maternal stress during pregnancy. Birthweight deficit-associated high BP has been recapitulated in gestationally undernourished and dexamethasone (Dex)-treated rats. We investigated the programming of high BP in rat offspring due to gestational undernutrition or exposure to diverse environmental chemicals. Pregnant rats were subjected to nutritional or chemical treatments previously demonstrated to induce slight maternal toxicity and/or a birthweight deficit: 50% undernutrition (GD 1-15 (UN1-15) or 10-21 (UN10-21)), Dex (0.2 mg/kg s.c., GD 14-20), atrazine (Atz; 125 mg/kg p.o., GD 14-20), perfluorooctane sulfonate (PFOS; 18.75 mg/kg p.o., GD 2-6), perfluorononanoic acid (PFNA; 5 mg/kg p.o., GD 1-20), nicotine (Nic; 6 mg/kg s.c., GD 2-20) or arsenic trioxide (As; 5 mg/kg p.o., GD 1-20). Offspring of treated dams were fostered to untreated dams at birth. Control dams were treated with the corresponding vehicle, route and duration. Litters were standardized to 8-10 pups/litter at birth. Systolic BP (SBP) was measured at 10-11 weeks of age by tail cuff photoplethysmography. Nephron counts were conducted in postnatal day (PND) 22 kidneys using confocal microscopy and Imaris software. A birthweight deficit was evident in the UN10-21, Dex, Atz, PFOS and PFNA, but not in the UN1-15, Nic or As groups, with catch-up growth occurring by PND 14. SBP in 10-11 week rats was increased in UN1-15, UN10-21, Dex and PFNA, but not Atz, PFOS, Nic or As groups. In 26 week adult rats, SBP was increased in the UN1-15 and UN10-21 groups (Dex, Atz, PFOS, PFNA and As groups are not of age yet). Nephron counts were lower in the UN1-15 and UN10-21 groups. These results suggest that programming of BP in juvenile and adult rats can be altered by either prenatal undernutrition or environmental chemical exposure. We are currently completing nephron counts and glucocorticoid and renin-angiotensin-aldosterone system gene expression to elucidate the mechanisms by which prenatal programming of adult hypertension occurs.