PHYSIOLOGICAL CONCENTRATIONS OF ESTRADIOL ATTENUATE ENDOTHELIN 1-INDUCED CORONARY VASOCONSTRICTION IN-VIVO

Background Estrogens are cardioprotective hormones and are reported to have antianginal properties. We examined the effect of physiological concentrations of 17 beta-estradiol on coronary reactivity in anesthet ized female farm pigs. Methods and Results Epicardial coronary cross-s ectional area (CSA) was assessed by two-dimensional intravascular ultr asound, average coronary peak flow velocity (APV) by intravascular Dop pler velocimetry, and coronary blood flow (CBF) was calculated. Dose-r esponse curves to intracoronary endothelin-l JET-I, 1 pmol/L to 10 nmo l/L), the selective ET, receptor agonist sarafotoxin (1 pmol/L to 10 n mol/L), and serotonin (0.1 nmol/L to 1 mu mol/L) were assessed before and after a 10-minute infusion of intracoronary estradiol (I nmol/ L). Before estradiol administration, ET-1 induced significant dose-depend ent decreases in CSA, APV, and CBF. Estradiol attenuated ET-1-induced epicardial vasoconstriction (P<.001) as well as ET-l-induced decreases in APV (P=.05) and CBF (P=.012). In an additional five pigs, vehicle (DMSO) had no effect on ET-l-induced coronary vasoconstriction. Before estradiol administration, sarafotoxin induced no net change in CSA bu t induced increases in APV and CBF, the extent of which did not change significantly after estradiol. Serotonin induced small decreases in C SA but increased APV and CBF. Estradiol did not influence serotonin-in duced changes in CSA: APV, or CBF. Conclusions We conclude that estrad iol attenuates ET-1-induced vasoconstriction, possibly through effects on the ETA receptor, because selective ETB receptor-induced stimulati on with sarafotoxin remained unchanged. Such an effect on the ETA rece ptor may relate to the antianginal properties of estrogens.