Ovariectomy regulates the production of prostanoids and the MAPK pathway in rat mesenteric arteries (LB675)

Abstract

Sex hormones regulate vascular function through nitric oxide (NO), thromboxane A2 (TXA2), and prostaglandin E2 (PGE2) among other factors. Since NO, TXA2 and PGE2 are known to regulate the epidermal growth factor receptor (EGFR) and downstream signaling pathways, the purpose of this study was to investigate whether the loss of ovarian function alters the production of these effectors regulating the activity of the mitogen‐activated protein kinase/extracellular‐regulated kinases 1 and 2 (MAPK‐ERK1/2), an EGFR downstream pathway. For this purpose, mesenteric arteries from control and ovariectomized Sprague‐Dawley rats (6‐months old) were used to analyze: i) the release of NO, TXA2 and PGE2; ii) the vascular reactivity to acetylcholine (Ach), the NO donor sodium nitroprusside, the TXA2‐mimetic compound U‐46619, and exogenous PGE2; and iii) the activation status of MAPK(ERK1/2). Our results show that ovariectomy: i) does not change NO release while decreases its vasodilator action; ii) increases the release and vasoconstrictor action of TXA2 and PGE2; and iii) increases the basal activity of the MAPK(ERK1/2) pathway. We conclude that activation of the EGFR/MAPK axis by these effectors could contribute to increase the proliferation rate of vascular smooth muscle cells, leading to increase peripheral resistance and hypertension.Grant Funding Source: Supported by the Fondo de Investigaciones Sanitarias (PI0011406) to MF.