Document Detail


Effects of BQ-123 on systemic and renal hemodynamic responses to endothelin-1 in the rat split hydronephrotic kidney.
MedLine Citation:
PMID:  9814615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To assess the site of action of endothelin-1 in vessels of different sizes in the kidney in vivo and investigate the function of endothelin A (ET(A)) receptors in mediating renal and systemic vasoconstriction. DESIGN: The luminal diameters of different vessels were measured and glomerular blood flow in cortical glomeruli was determined by intravital videomicroscopy in the split hydronephrotic kidney of anesthetized female Wistar rats. METHODS: The rats were infused with endothelin-1 (40 pmol/kg per min) with or without pretreatment with the selective ET(A)-receptor antagonist BQ-123 (0.5 mg/kg). Aortic clamping was used to control renal blood pressure during the endothelin-1 infusion. RESULTS: Exogenous endothelin-1 induced a significant rise (30+/-3%) in mean arterial pressure and a marked, long-lasting fall in glomerular blood flow (53+/-3%) related to reduction of the inner diameter of arcuate (-30%), interlobular arteries (-33%) and afferent arterioles (-17%). Aortic clamping to normalize renal blood pressure did not attenuate the vasoconstriction and reduction in glomerular blood flow. Pretreatment with BQ-123 significantly reduced both the endothelin-1-induced rise in mean arterial pressure (12+/-1%) and the fall in glomerular blood flow (-23+/-11%). BQ-123 blunted the response to endothelin-1 in arcuate (-12%), interlobular (-11%) and afferent vessels (-5%). Acetylcholine and nitroprusside completely reversed the vasoconstriction in BQ-123-pretreated animals. CONCLUSIONS: BQ-123 largely prevented the hemodynamic effects of exogenously administered endothelin-1. Our direct in-vivo techniques showed that ET(A) receptors are, at least in part, involved in endothelin-1 -mediated vasoconstriction in the rat kidney, and support the hypothesis that ET(A) receptors may help to control arterial pressure in anesthetized rats.
Authors:
A Cavarape; E Bartoli
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of hypertension     Volume:  16     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-01-11     Completed Date:  1999-01-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1449-58     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, University of Udine, Italy. alessandro.cavarape@dpmsc.uniud.it
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Flow Velocity / drug effects
Blood Pressure / drug effects
Drug Therapy, Combination
Endothelin-1 / pharmacology*
Female
Glomerular Filtration Rate / drug effects
Hydronephrosis / drug therapy,  pathology,  physiopathology*
Kidney Glomerulus / blood supply,  pathology,  physiopathology
Microscopy, Video
Peptides, Cyclic / pharmacology*
Rats
Rats, Wistar
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors*
Renal Artery / drug effects,  pathology,  physiopathology
Renal Circulation / drug effects*
Vasoconstriction / drug effects
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Peptides, Cyclic; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Vasodilator Agents; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu)

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