Anderson P G, Bishop S P, Digerness S B
Department of Pathology, University of Alabama, Birmingham 35294.
Circ Res. 1989 Jun;64(6):1127-36. doi: 10.1161/01.res.64.6.1127.
The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial and coronary vascular function and structure. Twelve-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with and without 12 weeks of vasodilator antihypertensive treatment (hydralazine) were studied using an isolated perfused rat heart model. Hydralazine treatment normalized blood pressure in SHR but did not cause regression of cardiac hypertrophy (heart weight to body weight ratio of SHR + hydralazine 4.33 +/- 0.098 vs. SHR 4.66 +/- 0.091; WKY 3.21 +/- 0.092 and WKY + hydralazine 3.38 +/- 0.152; mean +/- SEM). Coronary flow reserve, elicited by adenosine vasodilation in the perfused heart, was decreased in SHR (29%) compared with WKY (105%) and WKY + hydralazine (100%) and was significantly improved in SHR + hydralazine (75%). Morphometric evaluation of perfusion-fixed coronary arteries and arterioles (30-400 microns diameter) demonstrated a significant increase in the slope of the regression line comparing the square root of medial area versus outer diameter in SHR (0.444) compared with WKY (0.335) and WKY + hydralazine (0.336, p less than 0.05). Blood vessels from SHR + hydralazine were not different from control (0.338). Cardiac oxygen consumption was decreased in SHR (10.9 +/- 0.74 mumols oxygen/min/g/60 mm Hg left ventricular pressure) compared with WKY (22.4 +/- 1.47) and WKY + hydralazine (23.4 +/- 1.90; p less than 0.01), while SHR + hydralazine was intermediate (16.0 +/- 1.60). These studies suggest that significant alterations in myocardial and coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although moderate coronary deficits do remain after chronic antihypertensive therapy.
这些研究的目的是评估高血压诱导心肌肥厚模型中心血管结构和功能的变化，在该模型中血管扩张剂治疗可使血压降至正常水平。因此，我们确定了高血压和心肌肥厚对心肌及冠状血管功能和结构的单独影响。使用离体灌注大鼠心脏模型，对12月龄的自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto大鼠（WKY）进行研究，其中部分大鼠接受了12周的血管扩张剂降压治疗（肼屈嗪）。肼屈嗪治疗使SHR血压恢复正常，但未使心脏肥厚消退（SHR + 肼屈嗪的心脏重量与体重比为4.33±0.098，而SHR为4.66±0.091；WKY为3.21±0.092，WKY + 肼屈嗪为3.38±0.152；均值±标准误）。与WKY（105%）和WKY + 肼屈嗪（100%）相比，在灌注心脏中由腺苷血管舒张引起的SHR冠状动脉血流储备降低（29%），而SHR + 肼屈嗪的冠状动脉血流储备显著改善（75%）。对灌注固定的冠状动脉和小动脉（直径30 - 400微米）进行形态学评估显示，与WKY（0.335）和WKY + 肼屈嗪（0.336，p < 0.05）相比，SHR中比较中膜面积平方根与外径的回归线斜率显著增加（0.444）。SHR + 肼屈嗪的血管与对照组无差异（0.338）。与WKY（22.4±1.47）和WKY + 肼屈嗪（23.4±1.90；p < 0.01）相比，SHR的心脏耗氧量降低（10.9±0.74微摩尔氧气/分钟/克/60毫米汞柱左心室压力），而SHR + 肼屈嗪处于中间水平（16.0±1.60）。这些研究表明，高血压诱导的心脏肥厚会导致心肌和冠状血管结构及功能发生显著改变。冠状血管系统对血压有反应，独立于心脏肥厚，尽管慢性降压治疗后仍存在中度的冠状动脉功能缺陷。
