RGD Reference Report - Induction of renal 20-hydroxyeicosatetraenoic acid by clofibrate attenuates high-fat diet-induced hypertension in rats. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Induction of renal 20-hydroxyeicosatetraenoic acid by clofibrate attenuates high-fat diet-induced hypertension in rats.

Authors: Zhou, Y  Huang, H  Chang, HH  Du, J  Wu, JF  Wang, CY  Wang, MH 
Citation: Zhou Y, etal., J Pharmacol Exp Ther. 2006 Apr;317(1):11-8. Epub 2005 Dec 8.
RGD ID: 2303383
Pubmed: PMID:16339392   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.105.095356   (Journal Full-text)

This study compared renal hemodynamics, the expression of CYP4A isoforms [the enzymes for 20-hydroxyeicosatetraenoic acid (20-HETE) production], and tubular sodium transporters in male rats fed a high-fat (HF) or control diet for 10 weeks. We also studied the effect of treatment with clofibrate, a CYP4A inducer, on sodium retention and renal function and on CYP4A expression in HF rats. HF rats had higher blood pressure (BP), renal plasma flow, and glomerular filtration rate (GFR), but no significant change in renal vascular resistance. Reverse transcription-polymerase chain reaction analysis showed that CYP4A1 and CYP4A8 expression was significantly decreased in the renal cortex of HF rats. Western blot analysis showed up-regulation of expression of the alpha-subunit of the epithelial sodium channel (alpha-ENaC), the beta-subunit of the epithelial sodium channel (beta-ENaC), sodium/hydrogen exchanger (NHE)-3, and the renal outer medulla K(+) channel (ROMK) in HF rats, whereas expression of the gamma-subunit of the epithelial sodium channel and the alpha1-subunit of Na(+)-K(+)-ATPase remained unchanged. Thus, HF treatment caused the reduction of renal CYP4A1 and CYP4A8 expression, whereas the increases in alpha-ENaC, beta-ENaC, NHE-3, and ROMK expression in renal tubules may have contributed sodium retention and hypertension in HF rats. Furthermore, clofibrate treatment (240 mg/kg/day) caused the decrease of BP and GFR and the attenuation of cumulative sodium balance in HF rats. The attenuation of sodium retention by clofibrate treatment is linked to decreased expression of NHE-3 in renal cortex. Clofibrate induction of CYP4A expression occurred in proximal tubules and in the thick ascending limb of the loop of Henle but not in renal microvessels. This induction correlated with the expression of peroxisome proliferator-activated receptor (PPARalpha) in renal tubules. Therefore, these results suggest that the effects of clofibrate on sodium retention and blood pressure regulation in HF rats may be due to the induction of renal tubular 20-HETE production through the PPARalpha pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IEP 2303383; 2303383mRNA:decreased expression:kidney cortexRGD 
hypertension  ISOCyp4a1 (Rattus norvegicus)2303383mRNA:decreased expression:kidney cortexRGD 
hypertension  ISOCyp4a8 (Rattus norvegicus)2303383mRNA:decreased expression:kidney cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp4a1  (cytochrome P450, family 4, subfamily a, polypeptide 1)
Cyp4a8  (cytochrome P450, family 4, subfamily a, polypeptide 8)

Genes (Mus musculus)
Cyp4a10  (cytochrome P450, family 4, subfamily a, polypeptide 10)
Cyp4a12b  (cytochrome P450, family 4, subfamily a, polypeptide 12B)


Additional Information