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 17beta-estradiol on coronary reactivity in anesthetized female farm pigs.


RESULTS
Epicardial coronary cross-sectional area (CSA) was assessed by two-dimensional intravascular ultrasound, average coronary peak flow velocity (APV) by intravascular Doppler velocimetry, and coronary blood flow (CBF) was calculated. Dose-response curves to intracoronary endothelin-1 (ET-1, 1 pmol/L to 10 nmol/L), the selective ET(B) receptor agonist sarafotoxin (1 pmol/L to 10 nmol/L), and serotonin (0.1 nmol/L to 1 micromol/L) were assessed before and after a 10-minute infusion of intracoronary estradiol (1 nmol/L). Before estradiol administration, ET-1 induced significant dose-dependent decreases in CSA, APV, and CBF. Estradiol attenuated ET-1-induced epicardial vasoconstriction (P<.001) as well as ET-1-induced decreases in APV (P=.05) and CBF (P=.012). In an additional five pigs, vehicle (DMSO) had no effect on ET-1-induced coronary vasoconstriction. Before estradiol administration, sarafotoxin induced no net change in CSA but induced increases in APV and CBF, the extent of which did not change significantly after estradiol. Serotonin induced small decreases in CSA but increased APV and CBF. Estradiol did not influence serotonin-induced changes in CSA, APV, or CBF.


CONCLUSIONS
We conclude that estradiol attenuates ET-1-induced vasoconstriction, possibly through effects on the ET(A) receptor, because selective ET(B) receptor-induced stimulation with sarafotoxin remained unchanged. Such an effect on the ET(A) receptor may relate to the antianginal properties of estrogens.
Sudhir
K
K
Cardiology Division, University of California, San Francisco 94143, USA. sudhir@cardio.ucsf.edu
Ko
E
E
Zellner
C
C
Wong
H E
HE
Hutchison
S J
SJ
Chou
T M
TM
Chatterjee
K
K
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D018084:Ultrasonography, Interventional; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D014677:Pharmaceutical Vehicles; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D012701:Serotonin; D004958:Estradiol