Effect Of Heart Remodeling In DOCA-salt Hypertensive Rats Under The Intervention Of Antihypertensive Drugs

OBJECTIVES. This study was performed to observe the effect of heart remodeling and the express of MMP-2 /TIMP-2 in DOCA-salt Hypertensive Rats under the intervention of antihypertensive drugs, to evaluate the respective role of the increased arterial pressure and of humoral factors on cardiac remodeling and microvasulative density in an experimental hypertension, and to explore the role and significance of MMP-2 /TIMP-2 in the hearts of DOCA-salt Hypertensive Rats.Methods: Uninephrectomized rats received DOCA, a high salt diet, and they were treated for 5 weeks with either a long-acting calcium antagonist, amlodipine ( 20mg/kg. day-1), an ACE inhibitor, ramipril (3mg/kg. day-1), AT1 receptor antagonist, valsartan (35mg/kg. day-1) or a mixed ETA-ETB endothelin receptor antagonist, bosentan (100 mg/kg day-1). A group of hypertensive rats was left untreated and a sham-operated group of normotensive rats was used for control. At the end cf treatment, Cardiac hypertrophy and interstitial and perivascular fibrosis and microvasulative density as well as expression of MMP-2/TIMP-2 were evaluated by quantitative morphometry.RESULTS: DOCA-salt hypertensive rats exhibited a marked cardiac hypertrophy associated with a decrease of microvasulative density and interstitial and perivascular fibrosis and an increase of expression of MMP-2/TIMP-2.The calcium antagonist nearly normalized arterial pressure and suppressed all these changes. Ramipril or valsartan had no effect on arterial pressure and microvasulative density , but Ramipril decreased subendocardial fibrosis and perivascular fibrosis. Bosentan had a very small effect on arterial pressure but decreased cardiac hypenrophy and both perivascular and subendocardial fibrosis and microvasulative density and downregulated the expression ofMMP-2/TIMP-2.Conclusions: We conclude that in DOCA salt hypertension, humoral factors such asendothelin may play a role besides high blood pressure in cardiac remodeling. In addition, the different components of this remodeling (microvasulative density, cardiac hypertrophy and cardiac fibrosis) are controlled independently . MMP-2/TIMP-2 may play an important role in microvasulative change.