Okoshi M P, Matsubara L S, Franco M, Cicogna A C, Matsubara B B
Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brasil.
Braz J Med Biol Res. 1997 Sep;30(9):1135-44. doi: 10.1590/s0100-879x1997000900013.
The pathogenesis of fibrosis and the functional features of pressure overload 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 unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 +/- 19 mmHg and RHT8: 194 +/- 24 mmHg, P < 0.05 vs control: 123 +/- 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 +/- 0.38 micrograms/mg; RHT4: 3.02 +/- 0.40 micrograms/mg; RHT8: 3.44 +/- 0.45 micrograms/mg of dry tissue, P < 0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local, conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed by scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness.
纤维化的发病机制以及压力超负荷心肌肥大的功能特征仍存在争议。本研究的目的是评估肾血管性高血压（RHT）大鼠肥厚心肌的功能和形态。雄性Wistar大鼠在单侧肾缺血后第4周（RHT4）和第8周（RHT8）处死（Goldblatt II高血压模型）。正常血压大鼠用作对照。在离体乳头肌标本中分析心肌功能，通过光学显微镜确定形态学特征，并用分光光度法测定心肌羟脯氨酸浓度（HOP）。肾动脉夹闭导致收缩期动脉压升高（RHT4：178±19 mmHg，RHT8：194±24 mmHg，与对照组123±7 mmHg相比，P<0.05）。在两个肾血管性高血压组中均观察到心肌肥大。RHT8组心肌HOP浓度升高（对照组：2.93±0.38微克/毫克；RHT4：3.02±0.40微克/毫克；RHT8：3.44±0.45微克/毫克干组织，与对照组和RHT4组相比，P<0.05）。形态学研究表明，在整个实验期间均存在心肌细胞坏死、血管损伤和细胞炎症反应。小动脉外膜的细胞增多更为明显。由于心肌细胞坏死，早期出现局部结缔组织基质塌陷，嗜银间质纤维紊乱和增粗，随后形成瘢痕。功能数据显示RHT4组心肌被动僵硬度增加。我们得出结论，肾血管性高血压可导致心肌细胞和小动脉坏死。对坏死的炎症反应导致了修复性纤维化。离体乳头肌的力学行为正常，但早期心肌被动僵硬度增加。
