Document Detail


Increased salt sensitivity secondary to leptin resistance in SHHF rats is mediated by endothelin.
MedLine Citation:
PMID:  12619866     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A link between leptin resistance, obesity, and salt sensitivity has been suggested. SHHF/Mcc-fa(cp) rats (SHHF) were used to study the effect of gene dosage of a null mutation of the leptin receptor (cp) on salt sensitivity and response to a combined endothelin A and B receptor antagonist (bosentan). Obese (cp/cp), heterozygous (+/cp), and homozygous lean (+/+) male SHHF were fed a low salt diet (0.3% NaCl) for 7 days, followed by a high salt diet (8.0% NaCl) for 7 days. There were no significant differences in systolic blood pressure between genotypes on low salt. In response to high salt, cp/cp had significantly greater systolic pressure than +/cp and +/+. On high salt diet, cp/cp showed a significant increase in 24 h urinary endothelin excretion and increased renal expression of preproendothelin mRNA. There was no effect of high salt diet on renal excretion of nitric oxide (NOx) or on gene expression of endothelial, neuronal, or cytokine-induced nitric oxide synthase isoforms (eNOS, nNOS, iNOS, respectively). Treatment with bosentan prevented the high salt-induced increment in systolic blood pressure in cp/cp. This was associated with a doubling of renal NOx excretion, but without changes in eNOS, nNOS, or iNOS expression. Endothelin receptor antagonism did not normalize systolic pressure in any of the genotypes. Our studies indicate that obesity secondary to leptin resistance (cp/cp) results in increased salt sensitivity that is mediated by endothelin in the SHHF rat.
Authors:
M Judith Radin; Bethany J Holycross; Toni M Hoepf; Sylvia A McCune
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  242     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-03-06     Completed Date:  2003-10-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  57-63     Citation Subset:  IM    
Affiliation:
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA. radin.1@osu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects,  physiology
Body Weight / drug effects
Disease Models, Animal
Endothelins / metabolism,  pharmacology*
Hypertension / physiopathology
Kidney / drug effects,  physiopathology
Leptin / metabolism*
Male
Obesity / genetics,  metabolism
RNA, Messenger / genetics,  metabolism
Rats
Rats, Inbred SHR
Receptors, Endothelin / metabolism
Sodium Chloride, Dietary / administration & dosage,  metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Endothelins; 0/Leptin; 0/RNA, Messenger; 0/Receptors, Endothelin; 0/Sodium Chloride, Dietary

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