24 Analysis of left ventricular fibrosis in renovascular hypertensive rats: effect of losartan and spironolactone

INTRODUCTION:Myocardial fibrosis associated with arterial hypertension modifies myocardial function and structure. Using spironolactone (spiro), an aldosterone antagonist, and losartan (DuP 753), an angiotensin II antagonist, we attempted to elucidate the role played by these hormones in the establishment of myocardial fibrosis in the renovascular Goldblatt model (two-kidney, one clip). METHODS:Sixty-three male Wistar rats were used. Ten clipped rats and eleven age-matched controls were killed 1 month after the application of a renal clip. Eight other clipped rats received 20 mg/kg per day spiro per os, twelve received 20 mg/kg per day losartan and nine received placebo; all were killed 4 months after clipping, together with 13 controls. The left ventricles were removed and weighed. The total collagen content, including pericoronary and microscar coflagens, was estimated macroscopically (MacroColl) on paraffin sections stained with Sinus red. Otherwise, the fibrosis was estimated with polarization microscopy in which type I collagen (coll I) is orange-coloured and type III collagen (coll III) is green. Thus, using appropriate band-pass filters and computer-assisted morphometry, it was possible to quantitate each collagen. RESULTS:One month after clipping, and throughout the experiment, regardless of treatment, systolic blood pressure (SBP) and left ventricular hypertrophy (LV/BW) were significantly increased in the clipped groups. The MacroColl was significantly increased in the clipped groups. Losartan, unlike spiro, prevented this increase. The interstitial coll I and coll III densities (IntDens) were not increased in the untreated clipped rats. The coll III IntDens was lower in the spiro group than in all age-matched groups. The pericoronary coll III content weighed by the surface area of the artery (PeriColl III) was increased significantly from the first to the fourth month after clipping in all clipped rats except those treated with spiro. The increase in PeriColl I 4 months after clipping was prevented by losartan but not by spiro treatment (Table 1). CONCLUSIONS:Together with hypertension, aldosterone and angiotensin II play an important role on myocardial fibrosis, inducing respectively coll III and coll I synthesis, mainly around the coronary artery. Although the coll III precedes the coll I synthesis, coll III synthesis inhibition by spiro treatment did not affect coll I synthesis. This suggests that these two types of collagen have different me