Cardiac structure and function in a mouse model of uraemia without hypertension.
Kidney dysfunction is often associated with cardiac left ventricular hypertrophy and increased cardiovascular mortality.


OBJECTIVE
The aim of this study was to find out whether this reflects direct effects of uraemia on the heart or is dependent on accompanying hypertension.


METHODS
Apolipoprotein-E (apoE)-deficient C57BL/6 mice are resistant to development of hypertension after renal mass reduction. To evaluate the impact of uraemia without hypertension on the heart, apoE-deficient mice underwent 5/6 nephrectomy (NX) or sham operation (Sh) and were randomized to treatment with the angiotensin converting enzyme inhibitor enalapril (12 mg kg(-1) d(-1)) or no medication.


RESULTS
NX did not affect systolic blood pressure (BP), but reduced mean creatinine clearance, body weight and blood haemoglobin to 27% (p < 0.01), 82% (p < 0.0001) and 73% (p < 0.0001), respectively, of the values in Sh mice. Thirty-six weeks after NX, heart wet weight, echocardiographic estimates of left ventricular mass and left ventricular diastolic and systolic functions were similar in NX and Sh mice. NX did not increase cardiac fibrosis or cardiac mRNA expression of biglycan, whereas it decreased the mRNA expression of procollagen (p < 0.01). Enalapril reduced BP (p < 0.001), heart wet weight and estimated left ventricular mass in both NX (p < 0.01) and Sh mice (p < 0.05), but did not affect cardiac diastolic or systolic function. Conclusions. The results suggest that uraemia does not impair cardiac structure or function in apoE-deficient mice. Since NX has no effect on BP in apoE-deficient mice, the results may indicate that hypertension is important for development of left ventricular disease in uraemia.
Department of Nephrology, Rigshospitalet, Copenhagen, Denmark. susannebro@dadlnet.dk
Susanne
S
Bro
Entela
E
Bollano
Annemarie
A
Brüel
Klaus
K
Olgaard
Lars B
LB
Nielsen
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D004195:Disease Models, Animal; D004656:Enalapril; D005355:Fibrosis; D006321:Heart / Q000502:physiology* / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009392:Nephrectomy; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D014511:Uremia / Q000150:complications*
D001057:Apolipoproteins E; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A