Reactive and reparative myocardial fibrosis in arterial hypertension in the rat

Objective: Myocardial fibrosis is an important determinant of pathological hypertrophy. In two experimental models of arterial hypertension the purpose of the study was (a) to determine total collagen volume fraction and relative contribution of scarring and perivascular/interstitial fibrosis; and (b) to assess the effects of the aldosterone receptor antagonist spironolactone on these patterns of fibrosis. Methods: 76 eight week old Sprague-Dawley rats weighing 180 to 200 g were used for the studies. Using videodensitometry total collagen volume fraction was separated into the various components for the left and right ventricles in the following experimental models: renovascular hypertension occurring following unilateral renal ischaemia; continuous aldosterone administration via osmotic minipumps with either high (AL) or low (ALLO) sodium diet; renovascular hypertension and AL after pretreatment and continuous treatment with either 20 or 200 mg·kg−1·d−1 subcutaneously of the competitive aldosterone receptor antagonist spironolactone. All groups were compared to age and sex matched controls. Results: After eight weeks, systolic pressure was comparably increased in renovascular hypertension and AL and it remained raised with low dose spironolactone treatment in either model, but was normal with high dose spironolactone or low sodium diet. Left ventricular hypertrophy, expressed as a significant increase in left to right ventricular weight and left ventricle to body weight ratios, was present in renovascular hypertension, AL, and AL + low dose spironolactone compared to control (p