| Acute effects of toremifene on the vasculature of intact and menopause-induced rats. | |
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MedLine Citation:
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PMID: 14746827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Clinical studies have shown that cardiovascular performance in postmenopausal women could be modified by treatment with selective estrogen receptor modulators (SERM). However, the mechanisms by which these drugs act on the cardiovascular system have not been elucidated. This work evaluates the effect of toremifene, a new member of the SERM family, on the vasculature of intact and ovariectomized adult Sprague-Dawley rats. The responsiveness of rings from the thoracic aorta to norepinephrine, potassium chloride, acetylcholine and sodium nitroprusside was assessed before and after 15 min of incubation with 1.0-microM toremifene. Toremifene displaced the concentration-response curve for norepinephrine-induced contractions to the right in both groups of animals. Moreover, the EC(50) values for the curves increased from 154+/-31 to 754+/-162 nM (P<.05) in intact rats and from 88+/-11 to 230+/-71 nM (P<.05) in ovariectomized rats. Toremifene also reduced contractile responses to potassium chloride (10-120 mM), displacing the entire curve to the right in both groups of animals without modifying the EC(50) values. The drug shifted the concentration-response curve for the acetylcholine-induced relaxation to the left and significantly increased E(max) values (18% for ovariectomized rats vs. 16% for controls) without affecting EC(50) values in either group tested. In addition, toremifene potentiated the relaxing responses to physiological doses (0.1-1.0 nM) of sodium nitroprusside in both groups, suggesting a direct effect at the level of the vascular smooth muscle. Acute toremifene incubation increased basal relaxation in aortic rings from both intact and ovariectomized rats. These results suggest that toremifene, by improving the functional status of the endothelium-smooth muscle unit, may have a beneficial effect on the cardiovascular status of menopause-induced rats. |
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Authors:
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Jorge González-Pérez; María J Crespo |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Vascular pharmacology Volume: 40 ISSN: 1537-1891 ISO Abbreviation: Vascul. Pharmacol. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2004-01-28 Completed Date: 2004-05-25 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 101130615 Medline TA: Vascul Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 205-11 Citation Subset: IM |
Affiliation:
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Department of Biology, University of Puerto Rico-Rio Piedras, San Juan, Puerto Rico. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Animals Endothelium, Vascular / drug effects Estrogen Antagonists / pharmacology* Female Isometric Contraction / drug effects Muscle Contraction / drug effects Muscle Relaxation / drug effects Muscle, Smooth, Vascular / drug effects* NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide Synthase / antagonists & inhibitors Nitric Oxide Synthase Type III Nitroprusside / pharmacology Norepinephrine / pharmacology Ovariectomy* Potassium Chloride / pharmacology Rats Rats, Sprague-Dawley Toremifene / antagonists & inhibitors, pharmacology* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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2 S06 GM08224/GM/NIGMS NIH HHS; RR-03051/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogen Antagonists; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 50903-99-6/NG-Nitroarginine Methyl Ester; 51-41-2/Norepinephrine; 51-84-3/Acetylcholine; 7447-40-7/Potassium Chloride; 89778-26-7/Toremifene; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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