H e r z ~ ~rban & Vogel 1997 S. J. Hutchison*, K. Sudhir, T. M. Chou, K. Chatterjee Division of Cardiology, University of California, San Francisco Sex Hormones and Vascular Reactivity Summary It is increasingly recognized that sex steroids have, among many other effects, the ability to cause vasodilation. The vas- odilatory effects of estradiol have been the best documented and described. At low concentrations, estradiol has the ability to improve impaired endothelium dependent (nitric oxide mediated) relaxation in estrogen deficient subjects. At high concentrations, estradiol causes vasodilation principally by endothelium independent mechanisms, in a gender indepen- dent fashion, which appear to involve a number of pathways such as ATP-dependent K + channels. Testosterone also has ability, at higher doses, to cause vasodilation of the coronary circulation, in a gender independent fashion. The mecha- nisms of sex steroid-induced vasodilation are reviewed in this article. Key Words: Vasodilation 9 Estradiol - Testosterone 9 Coronary circulation Zusammenfassung: Vaskul~ireWirkungen weiblicher Geschlechtshormone Sexualhormone haben neben anderen Wirkungen auch die F~ihigkeit, Gef~13e zu dilatieren. Der vasodilatato;ische Effekt von ()stradiol ist am besten dokumentiert und be- schrieben worden. In niedrigen Konzentrationen verbessert Ostradiol die verminderte endothelabhfingige (NO-vermit- telte) Geffigdilatation bei Patienten mit C)strogenmangel. In hohen Konzentrationen verursacht Ostradiol eine Vasodila- tation ª einen endothelunabhgngigen Mechanismus, der geschlechtsunabhfingig ist und verschiedene Wege, unter anderem die ATP-abh~ingigen Kalziumkan~ile, benutzt. Testosteron hat ebenfalls in hoher Dosis die F~ihigkeit zu einer Vasodilatation, besonders der Koronargef~il3e. Auch dieser Effekt ist geschlechtsunabh~ingig. Der genaue Mecha- nismus der Vasodilatation, der durch die Sexualhormone induziert wird, wird in dieser Arbeit beschrieben. Schlª Vasodilatation - Ostradiol 9 Testosteron - Koronargef~ige A rising principally from observations of the favor- able impact of estrogens on coronary artery dis- ease (CAD), considerable interest has developed in the vascular effects of sex steroids. Most research has focused on estrogen and its effects, but there is now emerging evidence that many sex steroids are vasoac- tive. A wide range of such vasoactive effects has been described, in widely ranging preparations, and over broad dose ranges. Increasingly, studies are directed towards elucidating the modification of specific vasoac- tire pathways influenced by sex steroids. Observational studies of the relationship of estrogen lev- els to the incidence of CAD have established a favorable association of normal (premenopausal) estrogen levels with a lesser incidence of CAD events and death [1, 8,11, 30, 35, 36, 38, 49, 55, 64, 65, 74, 80, 84, 88]. It was initiatly *S. J. H. is partially funded by a traveling fellowship from the R. L. McLaughlin Foundation. Toronto, Canada. suggested that the decrease in CAD incidence was medi- ated through favorable alterations of CAD ¡ factors, such as reduced total cholesterol and LDL, elevated HDL, HDL2 and HDL3, lower insulin and glucose lev- els [95]. However, it is estimated that the observed mag- nitude of such modifications in risk factors can account for only 30 to 40% [63] of the observed reduction in CAD events and death. Therefore, other mechanisms must participate in the favorable impact of estrogens on the course of CAD. There is evidence that estrogens reduce atherogenesis in both human [28, 56, 87] and ani- mal studies [71, 82, 91-93], and that estrogens favorably influence platelet function [7], and coagulation [23]. As well, estrogenic and androgenic [106] compounds have been demonstrated to be arterial vasodilators. Arterial tone is determined by the net influence of vaso- constrictor and vasodilatory pathways, and on blood flow within the artery [47, 57]. Vasomotor tone is thus a dynamic physiologic entity - "vascular reactivity" - Herz 22 (1997), 141 - 150 (Nr. 3) 141