Miki Shigeyuki, Takeda Kazuo, Hatta Tsuguru, Harada Sanae, Kido Hidenori, Oguni Atsushi, Moriguchi Jiro, Morimoto Satoshi, Kawa Tetsuyoshi, Sasaki Susumu, Nakagawa Masao
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Am J Hypertens. 2002 Mar;15(3):286-90. doi: 10.1016/s0895-7061(01)02325-1.
The aim of this study was to compare the effect of angiotensin type-1 receptor blockade (ARB) on augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts with angiotensin converting enzyme (ACE) inhibitor, candesartan cilexetil (CAN) or enalapril was administered for 3 weeks in spontaneously hypertensive rats (SHR).
We used SHR (9 to 12 weeks old, n = 18) and Wistar-Kyoto (WKY) rats (n = 6). Systolic blood pressure was measured once a week. Spontaneously hypertensive rats were divided into three groups. Enalapril malate (10 mg/day) or CAN (10 mg/day) was administered orally in each of six SHR in each group receiving treatment for 3 weeks. The control group (n = 6) received no treatment. At the end of this experiment, the hearts were isolated. Isolated hearts mounted on a Langendorff apparatus after weighing were then perfused with modified Krebs-Henseleit buffer at constant pressure (75 mm Hg). The coronary perfusion pressure and coronary flow were measured during perfusion of isolated hearts. Coronary vascular resistance (CVR; mm Hg/mL/min/100 g) was calculated.
The ET-1 elicited increases in CVR dose-dependently in both normotensive and hypertensive rat hearts. However, the responses were significantly greater in SHR than in WKY rat. Chronic treatment with enalapril or candesartan inhibited the development of hypertension and cardiac hypertrophy equally in SHR. Augmented vasoconstrictive responses to ET-1 were significantly reduced in treated SHR. There was no difference in these effects between enalapril and candesartan.
These findings suggest that both ACE inhibitors and ARB can equally inhibit augmented coronary vascular response to ET-1 in hypertensive hearts.
本研究旨在比较血管紧张素1型受体阻滞剂（ARB）与血管紧张素转换酶（ACE）抑制剂对高血压心脏冠状动脉中内皮素-1（ET-1）增强的血管收缩反应的影响，将坎地沙坦酯（CAN）或依那普利给予自发性高血压大鼠（SHR）3周。
我们使用了9至12周龄的SHR（n = 18）和Wistar-Kyoto（WKY）大鼠（n = 6）。每周测量一次收缩压。将自发性高血压大鼠分为三组。每组6只SHR口服给予苹果酸依那普利（10 mg/天）或CAN（10 mg/天），治疗3周。对照组（n = 6）不接受治疗。实验结束时，分离心脏。称重后将离体心脏安装在Langendorff装置上，然后用改良的Krebs-Henseleit缓冲液在恒定压力（75 mmHg）下灌注。在离体心脏灌注期间测量冠状动脉灌注压和冠状动脉血流量。计算冠状动脉血管阻力（CVR；mmHg/mL/min/100 g）。
ET-1在正常血压和高血压大鼠心脏中均引起CVR剂量依赖性增加。然而，SHR中的反应明显大于WKY大鼠。依那普利或坎地沙坦的长期治疗在SHR中同样抑制高血压和心脏肥大的发展。治疗后的SHR中对ET-1增强的血管收缩反应明显降低。依那普利和坎地沙坦在这些作用上没有差异。
这些发现表明，ACE抑制剂和ARB均可同等程度地抑制高血压心脏中冠状动脉对ET-1增强的血管反应。
