Vasorelaxants Mechanisms of Estriol: Endothelium-Dependent and -Independent Pathways in an Ex Vivo Rat Aortic Model

Resumen

This study investigated the vasorelaxant effects of estriol (E3) compared to estradiol (E2) in rat thoracic aortic rings, focusing on endothelium-dependent and independent mechanisms. Isolated aortic rings from Wistar rats, with or without endothelium, were pre-contracted with phenylephrine and subjected to cumulative concentration–response curves for E3 and E2. The involvement of endothelial nitric oxide synthase (eNOS), potassium channels, prostanoids, and calcium influx was assessed using pharmacological inhibitors (L-NAME, TEA, indomethacin) and depolarizing Ca²⁺-free solutions. E3 promoted concentration-dependent vasorelaxation, but with lower potency and efficacy than E2. In endothelium-intact preparations, the relaxation induced by E3 was significantly reduced by L-NAME and TEA, suggesting participation of nitric oxide and potassium channels in its mechanism. Indomethacin did not alter E3-induced relaxation, indicating no significant involvement of prostanoids. In depolarized, calcium-free conditions, both E3 and E2 attenuated CaCl₂-induced contractions, indicating endothelium-independent modulation of calcium influx. These results demonstrate that estriol induces vasorelaxation through multiple mechanisms, including the activation of eNOS, involvement of K⁺ channels, and inhibition of calcium entry. Despite its lower efficacy, E3 shares key signaling pathways with E2 and may represent a vascularly active alternative in hormone replacement therapy with potentially favorable safety profiles.