Implication of chromosome 13 on hypertension and  associated disorders in Lyon hypertensive rats.
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.


CONCLUSIONS
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.
Gilibert
Sophie
S
Université de Lyon, Université Lyon1, Département de Physiologie et Pharmacologie Clinique, Faculté de Pharmacie, Lyon, France. sophie.gilibert@gmail.com
Bataillard
Alain
A
Nussberger
Juerg
J
Sassard
Jean
J
Kwitek
Anne E
AE
D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR / Q000235:genetics* / Q000502:physiology*; D012083:Renin / Q000097:blood; D012307:Risk Factors
D012083:Renin