title: Alike but not the same: anatomic heterogeneity of estrogen receptor-mediated vasodilation.
abstract: In view of recent findings on the anatomic heterogeneity of rapid vasodilation via estrogen receptor (ER)-dependent mechanisms, it is obvious that with regard to human physiology and disease much of it is still unknown, and research in this area is urgently needed. This is also important because chronic drug therapy with estrogens in women systemically affects the circulation and may affect certain arterial beds but not others. It is conceivable that the presence of any vascular disease (as was the case for coronary and carotid atherosclerosis in many of the patients in the large randomized controlled trials HERS and WHI) is likely to affect vascular responses to estrogens as well, and that any beneficial effects may be attenuated or even completely lost. Further work is required to decipher the mechanisms of vasodilation brought about by estrogens in humans and experimental animals, whether anatomic heterogeneity exists with regard to vascular beds and individual estrogen receptors, and how vascular disease (atherosclerosis in particular) affects responsiveness. Also, pharmacologcial tools for newly identified ERs are now available. The hypothesis that disease may modify or even abrogate estrogen-dependent or ER-selective vasodilation should also be tested. Finally, given that certain clinically approved drugs such as SERM or SERDs (thought only to block or downregulate nuclear ERs) actually cause vasodilation through GPER and have been shown in recent clinical studies to provide cardiovascular protection in postmenopausal women, we may have to rethink our current understanding, concepts, and strategies of how to interfere with the increased risk of vascular disease in women with estrogen deficiency or after menopause.
authors.affiliation: Molecular Internal Medicine, University of Zurich, Zurich, Switzerland. barton@access.uzh.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Meyer
authors.forename: Eric R
authors.initials: ER
authors.lastname: Prossnitz
mesh_terms: D002318:Cardiovascular Diseases / Q000517:prevention & control; D004967:Estrogens / Q000172:deficiency / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D011960:Receptors, Estrogen / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators