Document Detail


ET(A) receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats.
MedLine Citation:
PMID:  11408393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J B Park; E L Schiffrin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  37     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-15     Completed Date:  2001-08-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1444-9     Citation Subset:  IM    
Affiliation:
Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / 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:
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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