Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats. J Hypertens 2009 Jun;27(6):1186-93
Date
05/23/2009Pubmed ID
19462495Pubmed Central ID
PMC2915542DOI
10.1097/hjh.0b013e328329e4c0Scopus ID
2-s2.0-67649641497 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
BACKGROUND: Hypertension and associated disorders are major risk factors for cardiovascular disease. The Lyon hypertensive rat (LH) is a genetically hypertensive strain that exhibits spontaneous and salt-sensitive hypertension, exaggerated proteinuria, high body weight, hyperlipidemia, and elevated insulin-to-glucose ratio. Previous genetic mapping identified quantitative trait loci (QTLs) influencing blood pressure (BP) on rat chromosome 13 (RNO13) in several models of hypertension.
METHODS: To study the effects of a single chromosome on the mapped traits, we generated consomic strains by substituting LH RNO13 with that of the normotensive Brown Norway (BN) strain (LH-13BN) and reciprocal consomics by substituting a BN RNO13 with that of LH (BN-13LH). These reciprocal consomic strains, as well as the two parental strains were characterized for BP, metabolic and morphological parameters.
RESULTS: Compared with LH parents, LH-13BN rats showed decreased mean BP (up to -24 mmHg on 2% NaCl in the drinking water), urine proteins and lipids, and increased body weight. Differences between BN-13LH and BN rats were much smaller than those observed between LH-13BN and LH rats, demonstrating the effects of the highly resistant BN genome background. Plasma renin activity was not affected by the substitution of RNO13, despite the significant BP differences.
CONCLUSION: The present work demonstrates that RNO13 is a determinant of BP, proteinuria, and plasma lipids in the LH rat. The distinct phenotypic differences between the consomic LH-13BN and the LH make it a powerful model to determine genes and pathways leading to these risk factors for cardiovascular and renal disease.
Author List
Gilibert S, Bataillard A, Nussberger J, Sassard J, Kwitek AEAuthor
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Congenic
Blood Pressure
Cardiovascular Diseases
Chromosome Mapping
Disease Models, Animal
Humans
Hypertension
Kidney
Male
Quantitative Trait Loci
Rats
Rats, Inbred BN
Rats, Inbred SHR
Renin
Risk Factors