Endothelium‐independent relaxation induced by estrogen in the chicken ductus arteriosus

Abstract

Estrogen can modulate vascular tone by targeting both endothelial and/or vascular smooth muscle cells. However, The mechanism of estrogen‐induced vascular relaxation appears to be heterogeneous with respect to vessel and/or species. We aimed to characterize the vasoactive effects of estrogen in the chicken ductus arteriosus (DA). Isolated rings of the DA from 19‐d chicken fetuses (total incubation: 21‐d) were mounted in a wire myograph for isometric tension recordings. 17β‐estradiol elicited concentration‐dependent relaxation of KCl‐, phenylephrine‐, and oxygen‐induced active tone in male and female chicken DA. The stereoisomer 17a‐estradiol showed lesser relaxant effects. There were no gender differences in the responses to estrogen. Endothelium removal, or the presence of the soluble guanylate cyclase inhibitor ODQ, the K+ channels blockers glibenclamide and tetraethylammonium, or the estrogen receptor (ER) antagonist ICI 182,780 did not modify 17β‐estradiol‐induced relaxation. Preincubation (in normoxic, Ca2+‐free solution) of DA rings with 17β‐estradiol produced concentration‐dependent inhibition of the subsequent CaCl2‐induced contraction. ER‐α and ER‐β mRNAs (as determined by RT‐PCR) were strongly expressed in the ovary but ER‐α was weakly and ER‐β mRNA was not expressed in the DA. In conclusion, 17β‐estradiol induces endothelium‐independent relaxation of chicken DA, which is not mediated by ER activation. This relaxant effect is, at least partially, due to inhibition of Ca2+ entry from extracellular space.Supported by "Fundación de Investigación Médica Mutua Madrileña".