Regression of left ventricular hypertrophy in experimental renovascular hypertension: diastolic dysfunction depends more on myocardial collagen than it does on myocardial mass.
OBJECTIVE
To evaluate regression of experimental left ventricular hypertrophy (LVH) in terms of its effects both on myocardial collagen levels and on diastolic stiffness.


METHODS
Two-kidney, one clip Goldblatt hypertensive rats were left untreated for 4 weeks (HT4W, n = 12) or 12 weeks (HT12W, n = 11) and compared with rats the treatment of which was started after 4 weeks of hypertension with 30 mg/kg per day losartan for 8 weeks (LOS, n = 12), or 50 mg/l enalapril for 8 weeks (ENA, n = 11). A group of sham-operated rats served as controls (SHAM, n = 9).


RESULTS
The blood pressure of the rats increased significantly and LVH developed both after 4 and after 12 weeks of hypertension. Treatment with losartan or enalapril significantly decreased blood pressure and induced complete regression of LVH. Myocardial hydroxyproline concentrations increased in groups HT4W and HT12W (530 +/- 153 and 581 +/- 111 micrograms/g, respectively) relative to that in the SHAM group (421 +/- 22 micrograms/g). None of the treatments induced regression of increased myocardial collagen levels. The slopes of the end-diastolic stress-strain relationships in the isolated beating hearts were significantly higher in HT4W, HT12W and in both treated groups compared with those in the SHAM group, indicating increased diastolic myocardial stiffness.


CONCLUSIONS
Losartan and enalapril treatments decreased blood pressure and induced complete regression of LVH in this model of renovascular hypertension. In contrast, none of the treatments induced regression of increased myocardial collagen levels or reduced the abnormal left ventricular diastolic stiffness. These data suggest that diastolic dysfunction depends more on increased myocardial collagen levels than it does on myocardial mass in this model of pathological LVH.
Dussaillant
G R
GR
Pontificia Universidad Católica de Chile, Departamento de Enfermedades Cardiovasculares, Santiago, Chile.
Gonzalez
H
H
Cespedes
C
C
Jalil
J E
JE
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000032:analysis*; D003971:Diastole; D004656:Enalapril / Q000627:therapeutic use; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000627:therapeutic use
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D004656:Enalapril; D003094:Collagen; D019808:Losartan