MYOCARDIAL FIBROSIS RATHER THAN HYPERTROPHY INDUCES DIASTOLIC DYSFUNCTION IN RENOVASCULAR HYPERTENSIVE RATS

The aim of the present study was to evaluate the-effect of interstitia l fibrosis alone or associated with hypertrophy. on diastolic myocardi al function in renovascular hypertensive rats. Myocardial function was evaluated in isolated papillary muscle from renovascular hypertensive Wistar rats (RHT, n = 14), renovascular hypertensive rats treated wit h the angiotensin converting enzyme inhibitor (ACEI) ramipril, 20 mg.k g(-1).day(-1) (RHT RAM, n = 14), and age-matched unoperated and untrea ted Wistar rats (CONT, n = 12). The ACEI treatment for 3 weeks allowed the regression of myocyte mass and the maintenance of interstitial fi brosis. Myocardial passive stiffness was analyzed by the resting tensi on - length relationship. The myocardial fibrosis was evaluated by mea suring myocardial hydroxyproline (Hyp) concentration and by histologic al studies of the myocardium stained with hematoxylin and eosin or pic rosirius red. Left ventricular weight was significantly higher in RHT (0.97 +/- 0.12 g) compared with CONT (0.66 +/- 0.06 g) and RHT RAM (0. 69 +/- 0.14 g). The Hyp levels were 2.9 +/- 0.4, 3.4 +/- 0.3, and 3.8 +/- 0.4 mu g/mg of dry tissue for the CONT, RHT, and RHT RAM, respecti vely. Perivascular and interstitial fibrosis were observed in RHT and RHT RAM groups. There were lymphomononuclear inflammatory exudate and edema around arteries, involving adjacent myocytes in the RHT group. T here was an increased passive stiffness in RHT and RHT RAM groups comp ared with the CONT group. In conclusion, our results indicate that the Impaired diastolic function in the renovascular hypertensive rats is related to interstitial fibrosis rather than to myocardial hypertrophy .