INVESTIGADORES
SANCHEZ Angel Matias
congresos y reuniones científicas
Título:
Drospirenone increase endothelial nitric oxide synthesis via a combined action on progesterone and mineralocorticoid receptors.
Autor/es:
A.M. SANCHEZ; MI. FLAMINI; MS. GIRETTI; X. FU; L. GOGLIA; S. GARIBALDI; C. BALDACCI; P. MANELLA; A.R. GENAZZANI; T. SIMONCINI
Lugar:
May 19-23, Madrid, España
Reunión:
Congreso; 12th World Congress on the Menopause.; 2008
Institución organizadora:
INTERNATIONAL MENOPAUSE SOCIETY
Resumen:
Background: Progestins have actions on the cardiovascular system, which depend on the structure as well as on receptor binding characteristics. Drospirenone (DRSP) is a progestin that uniquely interferes with the signaling of the mineralocorticoid receptor (MR). Hormone therapy containing DRSP results in blood pressure reduction in hypertensive post-menopausal women. Objectives: We describe the effects of DRSP on endothelial nitric oxide (NO) synthesis and compare them with those of progesterone (P) and of medroxyprogesterone acetate (MPA) highlighting the differences in the signal transduction induced by these compounds through P and MRs. In addition, we herein tested the relevance of the anti-mineralocorticoid activity of DRSP for NO synthesis. Results: DRSP results in rapid activation of the endothelial NO synthase (eNOS) through mitogen activated protein kinases and phosphatidylinositol 3-kinase as well as in enhanced eNOS expression. These actions depend on P receptor. When the cells are exposed to aldosterone, a reduction of eNOS expression is found that is antagonized by DRSP. This action is not shared by P or MPA. In addition, DRSP does not interfere with the induction or activation of eNOS induced by estradiol, as opposed to MPA. Conclusions: In conclusion, we show that DRSP exerts a complex array of actions on human endothelial cells. Some of these effects are mediated by PRs but others depend on the interference with the MR. This unique mix of molecular actions on human endothelial cells sheds light on some of the actions of this compound on vascular function and help to interpret the anti-hypertensive effects of hormonal therapies containing DRSP.
