EXTRACELLULAR-MATRIX DEPOSITION IN HYPERTENSIVE HEARTS ANTIFIBROTIC EFFECTS OF RAMIPRIL

Hypertension induced in rats by suprarenal banding has a blood pressure elevating effect that is accompanied by the occurrence of cardiac hypertrophy and fibrosis. This phenomenon is already present at 2 weeks after banding and persists up to 1. 5 years. The increase in cardiac weight is mostly due to the development of fibrosis, since myocytes are only slightly increased in size. The fibrotic tissue consists mainly of fibronectin and collagen and contains numerous cellular elements. The occurrence of fibrosis can be completely inhibited by the administration of the specific ACE inhibiting drug, ramipril which indicated that angiotensin II may directly stimulate fibroblasts to produce fibronectin and collagen. The antifibrotic effect of ramipril was also present in a low dosage that did not lower blood pressure, confirming the hypothesis that angiotensin II has a direct effect on connective tissue cells and their ability to produce extracellular matrix proteins. The direct effect of the renin-angiotensin system on the activity of interstitial cells was further proven by molecular biology techniques showing an upregulation of transcription for collagen I and III which is prevented by ACE inhibition.