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L‐Arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt‐1 in pregnant rats
Author(s) -
Murphy Sydney,
Cockrell Kathy,
Granger Joey P.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1041.9
Subject(s) - medicine , endocrinology , preeclampsia , soluble fms like tyrosine kinase 1 , endothelin receptor , blood pressure , nitric oxide , endothelin 1 , pathogenesis , arginine , endothelins , chemistry , biology , pregnancy , receptor , biochemistry , placental growth factor , vascular endothelial growth factor , amino acid , genetics , vegf receptors
While soluble fms‐like tyrosine kinase (sFlt‐1) and endothelin (ET‐1) have been implicated in the pathogenesis of preeclampsia (PE), the mechanisms whereby increased sFlt‐1 leads to enhanced ET‐1 production and hypertension remain unclear. NO production is reduced in PE, however, whether a reduction in NO synthesis plays a role in increasing ET‐1 and blood pressure in response to chronic increases in plasma sFlt‐1 remains unclear. The purpose of this study was to determine the role of reduced NO synthesis is mediating the increase in blood pressure and ET‐1 in response to sFlt‐1 in pregnant rats. To achieve this goal, sFlt‐1 was infused into NP rats (3.7μg/kg/d for 6 days) and pregnant rats supplemented with 2% L‐arginine (in drinking water for 6 days). Infusion of sFlt‐1 into NP rats significantly elevated MAP (117±2 mmHg, p<0.05) versus NP (103±1 mmHg). sFlt‐1 hypertensive pregnant rats had ~3.5 fold increase in preproendothelin‐1 (PPET‐1) in the renal cortex when compared to NP rats. Supplementation with L‐arginine decreased the sFlt‐1 hypertension (108±3 mmHg, p<0.05) while having no effect on the blood pressure response in NP rats (108±2 mmHg), and abolished the enhanced sFlt‐1 induced PPET‐1 expression. In conclusion, a reduction in nitric oxide synthesis may play an important role in the enhanced ET‐1 production in response to sFlt‐1 hypertension in pregnant rats. NIH grant HL51971