Susic Dinko, Varagic Jasmina, Frohlich Edward D
Division of Research, Ochsner Clinic Foundation, New Orleans, Louisiana.
Ochsner J. 2008 Spring;8(1):5-10.
Purpose. This study was undertaken to examine adverse changes in coronary hemodynamics associated with hypertension, aging, and excessive salt intake. To dissociate from the possible effects of atherosclerosis, the study was done in rats because they do not develop atherosclerosis. Moreover, this strain of spontaneously hypertensive rats (SHR) develops hypertension similar to essential hypertension in man.Methods. Systemic and coronary hemodynamics, left ventricular mass, and collagen content in normotensive and SHR of various ages and given different treatments were determined.Results. Compared with normotensive Wistar-Kyoto rats, coronary blood flow reserve was lower and minimal coronary vascular resistance was higher in SHR of all ages; an age-related decrease in flow reserve and an increase in minimal vascular resistance were observed for both strains of rats. In very old rats with isolated systolic hypertension, an increase in left ventricular collagen was associated with coronary insufficiency; antihypertensive therapy nearly normalized both measures. In SHR excessive salt intake increased pressure, increased collagen deposition in myocardial interstitium and perivascularly, and impaired coronary circulation; angiotensin II receptor blocker therapy prevented fibrosis and improved coronary hemodynamics.Conclusion. In conclusion, these data indicate that considerable coronary insufficiency associated with hypertension, aging, and salt overload exists in the absence of atherosclerotic coronary changes. Perivascular fibrosis within myocardium may significantly contribute to the coronary vascular impairment.
目的。本研究旨在探讨与高血压、衰老及过量盐摄入相关的冠状动脉血流动力学的不良变化。为了排除动脉粥样硬化可能产生的影响,该研究选用大鼠进行,因为大鼠不会发生动脉粥样硬化。此外,这种自发性高血压大鼠(SHR)所患高血压与人类原发性高血压相似。
方法。测定了不同年龄且接受不同治疗的正常血压大鼠和SHR的全身及冠状动脉血流动力学、左心室质量和胶原蛋白含量。
结果。与正常血压的Wistar-Kyoto大鼠相比,各年龄段SHR的冠状动脉血流储备较低,最小冠状动脉血管阻力较高;两种品系的大鼠均观察到血流储备随年龄增长而降低,最小血管阻力随年龄增长而增加。在患有单纯收缩期高血压的老龄大鼠中,左心室胶原蛋白增加与冠状动脉供血不足有关;抗高血压治疗使这两项指标几乎恢复正常。在SHR中,过量盐摄入会使血压升高,增加心肌间质和血管周围的胶原蛋白沉积,并损害冠状动脉循环;血管紧张素II受体阻滞剂治疗可预防纤维化并改善冠状动脉血流动力学。
结论。总之,这些数据表明,在不存在动脉粥样硬化性冠状动脉病变的情况下,存在与高血压、衰老和盐负荷过重相关的严重冠状动脉供血不足。心肌内血管周围纤维化可能是导致冠状动脉血管损害的重要原因。