Specific inhibition of the contraction of the rat aorta by estradiol 17 beta.
Short-term exposure to estradiol 17 beta is known to inhibit the contraction of vascular smooth muscle preparations that is thought to be mediated by a [Ca++]-dependent mechanism. The purpose of this investigation was to examine the effect of prolonged exposure of vascular preparations to estradiol 17 beta to provide significant time for protein synthesis. We find that treatment of rat aortic rings with estradiol 17 beta (0.37-37 microM) for 15 to 180 min and subsequent removal of the estrogen by washing, attenuated the vasoconstrictor responses to phenylephrine and potassium chloride in a time-dependent manner. The maximum inhibitory effect took 120 min to develop. The inhibitory effect was endothelium independent and not blocked by the cyclooxygenase inhibitor, indomethacin, or by the endothelium derived relaxing factor inhibitor, Nw-nitro-L-arginine methyl ester. This effect was highly stereo-specific in that the 17 alpha isomer was significantly less potent than the 17 beta isomer of estradiol. Further, compared to other steroids, estradiol 17 beta was the most potent. The inhibitory effect of estradiol was blocked completely by pretreatment with the protein synthesis inhibitors, cycloheximide and puromycin, but not by actinomycin D. Electron microscopy showed an increase in ribosomal expression at the rough endoplasmic reticulum after incubation of the rat aorta with estradiol for 120 min. This indicates increased protein synthesis after exposure to estradiol 17 beta. We speculate that the time dependent inhibitory effect of estradiol 17 beta on vascular smooth muscle is related to protein synthesis at the translational level.
Thomas
G
G
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington DC, USA.
Ito
K
K
Zikic
E
E
Bhatti
T
T
Han
C
C
Ramwell
P W
PW
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000648:ultrastructure; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011500:Protein Synthesis Inhibitors; D010656:Phenylephrine; D009569:Nitric Oxide; D004958:Estradiol; D011189:Potassium Chloride; D013755:Tetradecanoylphorbol Acetate