Document Detail


Enhanced endothelin-1 response and receptor expression in small mesenteric arteries of insulin-resistant rats.
MedLine Citation:
PMID:  11158947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperinsulinemia, a primary feature of insulin resistance, is associated with increased endothelin-1 (ET-1) activity. This study determined the vascular response to ET-1 and receptor binding characteristics in small mesenteric arteries of insulin-resistant (IR) rats. Rats were randomized to control (C) (n = 32) or IR (n = 32) groups. The response to ET-1 was assessed (in vitro) in arteries with (Endo+) and without (Endo-) endothelium. In addition, arteries (Endo+) were pretreated with the ET(B) antagonist A-192621 or the ET(A) antagonist A-127722. Finally, binding characteristics of [(125)I]ET-1 were determined. Results showed that in Endo+ arteries the maximal relaxation (E(max)) to ET-1 was similar between C and IR groups; however, the concentration at 50% of maximum relaxation (EC(50)) was decreased in IR arteries. In Endo- arteries, the E(max) to ET-1 was enhanced in both groups. Pretreatment with A-192621 enhanced the E(max) and EC(50) to ET-1 in both groups. In contrast, A-127722 inhibited the ET-1 response in all arteries in a concentration-dependent manner; however, a greater ET-1 response was seen at each concentration in IR arteries. Maximal binding of [(125)I]ET-1 was increased in IR versus C arteries although the dissociation constant values were similar. In conclusion, we found the vasoconstrictor response to ET-1 is enhanced in IR arteries due to an enhanced expression of ET receptors and underlying endothelial dysfunction.
Authors:
P V Katakam; J S Pollock; D M Pollock; M R Ujhelyi; A W Miller
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  280     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H522-7     Citation Subset:  IM    
Affiliation:
University of Georgia College of Pharmacy, Augusta, Georgia 30912-3910, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight
Dose-Response Relationship, Drug
Endothelin-1 / biosynthesis,  metabolism*
Hyperinsulinism / metabolism*
Insulin Resistance / physiology*
Iodine Radioisotopes / diagnostic use
Male
Mesenteric Arteries / drug effects,  metabolism*
Muscle, Smooth, Vascular / drug effects,  metabolism
Pyrrolidines / pharmacology
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A
Receptor, Endothelin B
Receptors, Endothelin / antagonists & inhibitors,  biosynthesis,  metabolism*
Chemical
Reg. No./Substance:
0/A 192621; 0/Endothelin-1; 0/Iodine Radioisotopes; 0/Pyrrolidines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Receptors, Endothelin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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