| Enhanced endothelin-1 response and receptor expression in small mesenteric arteries of insulin-resistant rats. | |
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MedLine Citation:
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PMID: 11158947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P V Katakam; J S Pollock; D M Pollock; M R Ujhelyi; A W Miller |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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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:
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Created Date: 2001-02-22 Completed Date: 2001-03-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H522-7 Citation Subset: IM |
Affiliation:
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University of Georgia College of Pharmacy, Augusta, Georgia 30912-3910, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/A 192621; 0/Endothelin-1; 0/Iodine Radioisotopes; 0/Pyrrolidines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Receptors, Endothelin |
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