Vascular effects of ovariectomy and chronic oestrogen treatment in rats: controversy or experimental protocol diversity?
Several clinical studies have indicated that oestrogens have protective properties on the cardiovascular system. Although the beneficial effect has been attributable, at least in part, to their ability to stimulate the endothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the underlying mechanism still remains unclear. In a study from this issue of British Journal of Pharmacology, Nawate et al. have examined the effects of rat ovariectomy and chronic treatment with 17beta-oestradiol on the endothelial function as assessed ex vivo. The data indicate that acetylcholine-induced endothelium-dependent relaxations of the isolated mesenteric artery are affected by neither ovariectomy nor chronic hormonal treatment. Despite the maintained endothelium-dependent relaxation, the contribution of the two major endothelial factors NO and EDHF was changed. Indeed, ovariectomy increased the NO-mediated component of the relaxation, most likely as a consequence of the downregulation of the physiological allosteric inhibitor of endothelial NO synthase, caveolin-1. In addition, ovariectomy decreased the EDHF-mediated component of the relaxation and membrane hyperpolarization of the smooth muscle cells, an effect which might be explained by a concomitant decrease of the expression of the gap junction connexin-40 and connexin-43. Furthermore, chronic administration of 17beta-estradiol to ovariectomized rats normalized all these effects. This study provides further experimental evidence indicating that the hormonal status plays a determinant role in the control of the endothelial formation of both NO and EDHF.
Chataigneau
Thierry
T
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Strasbourg, France.
Schini-Kerth
Valérie B
VB
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004967:Estrogens / Q000008:administration & dosage*; D006801:Humans; D010052:Ovariectomy; D012107:Research Design / Q000592:standards*
D004967:Estrogens