MYOCYTE NECROSIS IS THE BASIS FOR FIBROSIS IN RENOVASCULAR HYPERTENSIVE RATS

The pathogenesis of fibrosis and the functional features of pressure o verload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT4) and 8 (RHT8) after u nilateral renal ischemia (Goldblatt II hypertension model). Normotensi ve rats were used as controls. Myocardial function was analyzed in iso lated papillary muscle preparations, morphological features were defin ed by light microscopy, and myocardial hydroxyproline concentration (H OP) was determined by spectrophotometry. Renal artery clipping resulte d in elevated systolic arterial pressure (RHT4: 178 +/- 19 mmHg and RH T8: 194 +/- 24 mmHg, P<0.05 vs control: 123 +/- 7 mmHg). Myocardial hy pertrophy was observed in both renovascular hypertensive groups. The m yocardial HOP concentration was increased in the RHT8 group (control: 2.93 +/- 0.38 mu g/mg; RHT4: 3.02 +/- 0.40 mu g/mg; RHT8: 3.44 +/- 0.4 5 mu g/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morph ological study demonstrated myocyte necrosis, vascular damage and cell ular inflammatory response throughout the experimental period. The inc reased cellularity was more intense in the adventitia of the arteriole s. As a consequence of myocyte necrosis, there was an early, local, co njunctive stroma collapse with disarray and thickening of the argyroph ilic interstitial fibers, followed by scarring. The functional data sh owed an increased passive myocardial stiffness in the RHT4 group. We c onclude that renovascular hypertension induces myocyte and arteriole n ecrosis. Reparative fibrosis occurred as a consequence of the inflamma tory response to necrosis. The mechanical behavior of the isolated pap illary muscle was normal, except for an early increased myocardial pas sive stiffness.