Makino N, Sugano M, Otsuka S, Hata T
Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Hypertension. 1997 Oct;30(4):796-802. doi: 10.1161/01.hyp.30.4.796.
We administered angiotensin (Ang) II receptor type 1 (AT1) blockade (losartan; 10 or 40 mg/kg per day), type II receptor (AT2) blockades (PD123319; 100 mg/kg per day), or angiotensin-converting enzyme (ACE) inhibitor (enalapril; 30 mg/kg per day) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. At the end of the treatment, high doses of losartan and enalapril significantly reduced the arterial systolic blood pressure compared with the untreated SHR to the level of WKY rats. But low doses of losartan and PD123319 were without effect. High doses of losartan and enalapril also significantly reduced both the left ventricular (LV) weight and the ratio of LV to body weight compared with the untreated SHR, which were still larger than that of WKY rats. However, the collagen concentration of SHR treated with high doses of losartan or enalapril was completely reduced to the level of WKY rats. Using reverse transcription polymerase chain reaction, we examined the mRNA expression for ACE, AT1, and AT2 in experimental animals. The enhanced AT1 mRNA expression was significantly decreased in the SHR treated with a high dose of losartan or PD123319 compared with the untreated SHR. The level of ACE mRNA was also decreased in the SHR treated with a high dose of losartan or enalapril. The level of AT2 mRNA was not significantly different between the Wistar-Kyoto rats and the SHR; however, this expression was decreased significantly after the treatment with a high dose of losartan or PD123319. These results indicate that AT1 receptor and ACE, but not AT2 receptor, play a crucial role in the remodeling of matrix tissue but a smaller role in the development of the hypertrophy of LV myocyte in SHR and that the LV/body weight changes do not fully account for the complete suppression of hypertension.
我们从10至20周龄开始，给自发性高血压大鼠（SHR）施用1型血管紧张素（Ang）II受体（AT1）阻滞剂（氯沙坦；每天10或40毫克/千克）、II型受体（AT2）阻滞剂（PD123319；每天100毫克/千克）或血管紧张素转换酶（ACE）抑制剂（依那普利；每天30毫克/千克）。治疗结束时，与未治疗的SHR相比，高剂量的氯沙坦和依那普利显著降低了动脉收缩压，降至WKY大鼠的水平。但低剂量的氯沙坦和PD123319无效。与未治疗的SHR相比，高剂量的氯沙坦和依那普利还显著降低了左心室（LV）重量以及LV与体重的比值，不过仍高于WKY大鼠。然而，用高剂量氯沙坦或依那普利治疗的SHR的胶原蛋白浓度完全降至WKY大鼠的水平。我们使用逆转录聚合酶链反应，检测了实验动物中ACE、AT1和AT2的mRNA表达。与未治疗的SHR相比，高剂量氯沙坦或PD123319治疗的SHR中增强的AT1 mRNA表达显著降低。高剂量氯沙坦或依那普利治疗的SHR中ACE mRNA水平也降低。Wistar-Kyoto大鼠和SHR之间的AT2 mRNA水平无显著差异；然而，用高剂量氯沙坦或PD123319治疗后，这种表达显著降低。这些结果表明，在SHR中，AT1受体和ACE在基质组织重塑中起关键作用，但在LV心肌细胞肥大发展中起较小作用，并且LV/体重变化不能完全解释高血压的完全抑制。
