Effect of acute and long-term treatment with 17-beta-estradiol on the vasomotor responses in the rat aorta.
1. This study sought to evaluate whether the effects of acute and long-term treatment with 17-beta-estradiol on the vasomotor responses in rat aortic rings are mediated through the same mechanism. 2. Ovariectomized rats were treated daily with either 17-beta-estradiol-3-benzoate (100 microg kg(-1)) or vehicle for 1 week. 3. The effect of long-term 17-beta-estradiol treatment on the responses to cumulative doses of phenylephrine, 5-HT, calcium, potassium and 17-beta-estradiol was determined in aortic rings. In the same rings, the effect of acute exposure to 17-beta-estradiol (5 and 10 microM) on the dose response curves for phenylephrine, 5-HT, calcium, potassium and acetylcholine were estimated. The measurements were made in rings with and without intact endothelium. The tone-related basal release of nitric oxide (NO) was measured in rings with intact endothelium. 4. Long-term 17-beta-estradiol treatment reduced the maximum developed contraction to all contracting agents studied. This effect was abolished in endothelium denuded vessels. Acute 17-beta-estradiol treatment also reduced maximal contraction. This effect, however, was independent of the endothelium. 5. Long-term 17-beta-estradiol treatment significantly increased the ability of the rings to dilate in response to acetylcholine whereas acute exposure to 17-beta-estradiol had no effect. The tone-related release of NO was significantly increased after long-term exposure to 17-beta-estradiol. 6. In conclusion, this study indicate that the acute and long-term effects of 17-beta-estradiol in the rat aorta are mediated through different mechanisms. The long-term effect is mediated through the endothelium most likely by increasing NO release. In contrast, the acute effect of 17-beta-estradiol seems to be through an effect on the vascular smooth muscle cells.
Andersen
H L
HL
Department of Preclinical Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
Weis
J U
JU
Fjalland
B
B
Korsgaard
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D004958:Estradiol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester