title: Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia.
abstract: Aldosterone levels are markedly elevated during normal pregnancy but fall even though volume contracts when preeclampsia occurs. The level of aldosterone in either condition cannot be explained solely by the activity of the renin-angiotensin II system. In normal gestation, vascular endothelial growth factor (VEGF) is thought to maintain vascular health, but its role in adrenal hormone production is unknown. We hypothesized that the role of VEGF in the adrenal gland is to maintain vascular health and regulate aldosterone production. Here, we demonstrate that supernatant of endothelial cells grown in the presence of VEGF enhanced aldosterone synthase activity in human adrenocortical cells. VEGF either alone or combined with angiotensin II increased aldosterone production in adrenal cells. These data suggest that endothelial cell-dependent and independent activation of aldosterone is regulated by VEGF. In contrast to angiotensin II, VEGF did not upregulate the steroidogenic acute regulatory protein. Consistent with this observation, angiotensin II stimulated both aldosterone and cortisol synthesis from progesterone, whereas VEGF stimulated selectively aldosterone production. In rats, overexpression of soluble fms-like tyrosine kinase-1, an endogenous VEGF inhibitor, led to adrenocortical capillary rarefaction and fall in aldosterone concentrations that correlated inversely with soluble fms-like tyrosine kinase-1 levels. These findings may explain why aldosterone increases so markedly during normal gestation and why preeclampsia, a condition characterized by high soluble fms-like tyrosine kinase-1, is associated with inappropriately low aldosterone levels in spite of relatively lower plasma volumes.
authors: Department of Nephrology, Hypertension and Clinical Pharmacology, University Hospital Bern, Berne, Switzerland.
authors: Carine
authors: C
authors: Gennari-Moser
authors: Eliyahu V
authors: EV
authors: Khankin
authors: Geneviève
authors: G
authors: Escher
authors: Fiona
authors: F
authors: Burkhard
authors: Brigitte M
authors: BM
authors: Frey
authors: S Ananth
authors: SA
authors: Karumanchi
authors: Felix J
authors: FJ
authors: Frey
authors: Markus G
authors: MG
authors: Mohaupt
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D023421:Models, Animal; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1