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Am J Physiol Renal Physiol. 2014 May 15;306(10):F1121-35. doi: 10.1152/ajprenal.00042.2014. Epub 2014 Mar 19.

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

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Departments of Physiology and Functional Genomics and Obstetrics and Gynecology, D. H. Barron Reproductive and Perinatal Biology Research Program, University of Florida College of Medicine, Gainesville, Florida; and
Institute of Cellular Medicine and Royal Victoria Infirmary, Newcastle University and Newcastle Hospitals National Health Service Foundation Trust, Newcastle Upon Tyne, United Kingdom.


During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced Kf and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure.


assisted reproductive technology; glomerular endotheliosis; glomerular filtration; heart failure; nitric oxide; osmoregulation; relaxin; renal hemodynamics; soluble vascular endothelial growth factor receptor-1

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