P326Regulation by androgens of umbilical artery tone of normotensive and hypertensive pregnant women

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Abstract

In the last decades several investigators have suggested the association of androgens with hypertension. Recently, some studies have shown that the incidence of cardiovascular diseases is increased in men with low testosterone levels, suggesting a protective role of androgens. Hypertension is one of the most common problems in pregnancy that complicates 5-10 % of pregnancies. An increase of morbidity was observed in babies from pregnant women with hypertension. However, the pathogenesis remains unclear and this limits the ability to prevent and treat this pathology. The beneficial effects of androgens for vascular system are associated with their ability to cause vasorelaxation. In human vessels, this non genomic effect of androgens appear to be due to activation of large conductance calcium-activated potassium channels (BKCa) and voltage gated potassium channels (KV) which is induced by cGMP increase and a consequent activation of cGMP-dependent protein kinase (PKG). On the other hand, the genomic effects of androgens concerning ionic channels are almost unknown. Our previous studies suggested that androgens increase the expression of BKCa channels and decrease expression of L-type calcium channels (LTCC). The aim of this work was to analyze the genomic effects of androgens on the expression of other proteins involved in the regulation of vascular contractility, such as soluble guanylate cyclase (sGC), the natriuretic peptide receptor-A (NPRA) and PKG. This study also aimed to compare the expression levels of these proteins in human umbilical artery (HUA) from normotensive and hypertensive pregnant women. To achieve these goals real time PCR was performed using smooth muscle cells of HUA pre-incubated for 24 hours with DHT (1-1000nM) or not (control). In the cells from normotensive pregnant women, androgens caused a decreased expression of sGC and PKG and an increase in the NPRA expression. However, in HUA muscle cells from pregnant hypertensive women, androgens cause a decrease in expression of sGC and NPRA and an increased expression of PKG. In summary, DHT modulates differently the expression of the analyzed proteins in normotensive and hypertensive pregnant women, which suggest that androgens could play an important role in hypertension.

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