期刊
SEMINARS IN NEPHROLOGY
卷 31, 期 1, 页码 15-32出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.semnephrol.2010.10.003
关键词
Placenta; decidualization; trophoblast; artery; renal circulation; nitric oxide; endothelin; matrix metalloproteinases; angiogenic growth factors
资金
- National Institutes of Health [RO1 HD030325, RO1 DK063321, RO1 HL067937, R21 HL093334]
- American Heart Association [0855090E]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD030325] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R21HL093605, R01HL067937] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK063321] Funding Source: NIH RePORTER
Relaxin is an approximately 6-kilodalton peptide hormone secreted by the corpus luteum, and circulates in the maternal blood during pregnancy. Relaxin administration to awake, chronically instrumented, nonpregnant rats mimics the vasodilatory, phenomena of pregnancy. Furthermore, immunoneutralization of relaxin or its elimination from the circulation during midterm pregnancy in awake rats prevents maternal systemic and renal vasodilation, and the increase in global arterial compliance. Human investigation, albeit limited through 2010, also reveals vasodilatory effects of relaxin in the nonpregnant condition and observations consistent with a role for relaxin in gestational renal hyperfiltration. Evidence suggests that the vasodilatory, responses of relaxin are mediated by its major receptor, the relaxin/insulin-like family peptide 1 receptor, RFXP1. The molecular mechanisms of relaxin vasodilation depend on the duration of hormone exposure (ie, there are rapid and sustained vasodilatory, responses). Newly emerging data support the role of G alpha(i/o) protein coupling to phosphatidylinositol-3 kinase/Akt (protein kinase B)-dependent phosphorylation and activation of endothelial nitric oxide synthase in the rapid vasodilatory responses of relaxin. Sustained vasodilatory responses critically depend on vascular endothelial and placental growth factors, and increases in arterial gelatinase(s) activity. Gelatinases hydrolyze big endothelin (ET) at a gly-leu bond to form ET1-32, which activates the endothelial ETB/nitric oxide vasodilatory pathway. Although the relevance of relaxin biology to preeclampsia is largely speculative at this time, there are potential tantalizing links that are discussed in the context of our current understanding of the etiology and pathophysiology of the disease. Semin Nephrol 31:15-32 (C) 2011 Elsevier Inc. All rights reserved.
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