Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 309, Issue 1, Pages R62-R70Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00377.2014
Keywords
pregnancy; hypertension; proteinuria; uterine artery resistance; animal model; superimposed preeclampsia; TNF-alpha; HIF-1 alpha; sFLT-1
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK095018]
- National Institute of General Medical Sciences [P20GM104357]
- National Heart, Lung, and Blood Institute [T32HL105324, R01HL094446]
- American Heart Association (AHA) [SDG 12SDG9440034, AHA 15PRE22660009]
- UMMC Intramural Research Support Program
- Robert M. Hearin Foundation
- Data Sciences International (DSI)/American Physiological Society
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The mechanisms of the pathogenesis of preeclampsia, a leading cause of maternal morbidity and death worldwide, are poorly understood in part due to a lack of spontaneous animal models of the disease. We hypothesized that the Dahl salt-sensitive (S) rat, a genetic model of hypertension and kidney disease, is a spontaneous model of superimposed preeclampsia. The Dahl S was compared with the Sprague-Dawley (SD) rat, a strain with a well-characterized normal pregnancy, and the spontaneously hypertensive rat (SHR), a genetic model of hypertension that does not experience a preeclamptic phenotype despite preexisting hypertension. Mean arterial pressure (MAP, measured via telemetry) was elevated in the Dahl S and SHR before pregnancy, but hypertension was exacerbated during pregnancy only in Dahl S. In contrast, SD and SHR exhibited significant reductions in MAP consistent with normal pregnancy. Dahl S rats exhibited a severe increase in urinary protein excretion, glomerulomegaly, increased placental hypoxia, increased plasma soluble fms-like tyrosine kinase-1 (sFlt-1), and increased placental production of tumor necrosis factor-alpha (TNF-alpha). The Dahl S did not exhibit the expected decrease in uterine artery resistance during late pregnancy in contrast to the SD and SHR. Dahl S pups and litter sizes were smaller than in the SD. The Dahl S phenotype is consistent with many of the characteristics observed in human superimposed preeclampsia, and we propose that the Dahl S should be considered further as a spontaneous model to improve our understanding of the pathogenesis of superimposed preeclampsia and to identify and test new therapeutic targets for its treatment.
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