Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia

Gennari-Moser, Carine; Khankin, Eliyahu V; Escher, Geneviève; Burkhard, Fiona; Frey, Brigitte M; Karumanchi, S Ananth; Frey, Felix J; Mohaupt, Markus G (2013). Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia. Hypertension, 61(5), pp. 1111-7. Philadelphia, Pa.: Lippincott Williams & Wilkins 10.1161/HYPERTENSIONAHA.111.00575

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Frey, Brigitte and Mohaupt, Markus

ISSN:

0194-911X

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Markus Georg Mohaupt

Date Deposited:

04 Oct 2013 14:42

Last Modified:

26 Feb 2014 04:37

Publisher DOI:

10.1161/HYPERTENSIONAHA.111.00575

PubMed ID:

23460276

Web of Science ID:

000317718200040

URI:

https://boris.unibe.ch/id/eprint/17478 (FactScience: 225258)

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