| ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats. | |
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MedLine Citation:
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PMID: 11408393 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased endothelin-1 may be associated with elevation of blood pressure (BP) and promotion of vascular hypertrophy, especially in salt-sensitive hypertension. Mineralocorticoid hypertension has been associated with activation of the endothelin system. We evaluated whether in aldosterone-infused rats the selective endothelin type A receptor-antagonist BMS 182874 prevents BP elevation and vascular hypertrophy. Rats were infused with aldosterone (0.75 microg/h) subcutaneously via a mini-osmotic pump and were offered 1% NaCl in the drinking water+/-BMS 182874 (40 mg/kg in food) for 6 weeks. Systolic BP was monitored by the tail-cuff method, and vascular changes of mesenteric arteries were evaluated using a pressurized myograph. Aldosterone-infusion significantly increased BP to 151+/-7 mm Hg compared with controls (108+/-4 mm Hg, P<0.01). BMS 182874 normalized BP (117+/-4 mm Hg). Media cross-sectional area of aorta was significantly increased by aldosterone infusion (P<0.05), and BMS treatment normalized it (P<0.001). Aldosterone infusion increased media width and media-to-lumen ratio of mesenteric resistance arteries (17.6+/-0.4 microm and 7.5+/-0.4%) compared with controls (14.2+/-0.5 microm, P<0.01, and 5.9+/-0.1%, P<0.05). BMS 182874 normalized media and media-to-lumen ratio (15.1+/-0.6 microm and 5.7+/-0.1%, both P<0.01). In conclusion, the endothelin type A receptor antagonist attenuated BP elevation and prevented vascular remodeling or hypertrophy of aorta and mesenteric resistance arteries in aldosterone-infused rats. These results suggest a role for endothelin-1 in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension. |
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Authors:
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J B Park; E L Schiffrin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hypertension Volume: 37 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-06-15 Completed Date: 2001-08-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1444-9 Citation Subset: IM |
Affiliation:
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Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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administration & dosage Animals Antihypertensive Agents / therapeutic use* Aorta / drug effects, metabolism, pathology Blood Pressure / drug effects* Body Weight / drug effects Dansyl Compounds / therapeutic use* Endothelin-1 Endothelins / biosynthesis, blood, genetics Hypertension / chemically induced, drug therapy*, pathology*, physiopathology Hypertrophy / chemically induced, drug therapy, pathology Infusions, Parenteral Male Mesenteric Arteries / drug effects, pathology, physiopathology Potassium / blood Protein Precursors / biosynthesis, genetics RNA, Messenger / biosynthesis Rats Rats, Sprague-Dawley Receptor, Endothelin A Receptors, Endothelin / antagonists & inhibitors* Vasoconstriction / drug effects Vasodilation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Dansyl Compounds; 0/Endothelin-1; 0/Endothelins; 0/Protein Precursors; 0/RNA, Messenger; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 153042-42-3/5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide; 52-39-1/Aldosterone; 7440-09-7/Potassium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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