Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats
Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats
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DOI：
10.1291/hypres.28.457
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
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作者：
Kirimura, K;Takai, S;Miyazaki, M
自发性高血压大鼠（SHR）血管平滑肌细胞表达血管紧张素ii形成乳糜酶（rat Vascular chymase [RVCH]），可能参与血压调节。在这项研究中，我们研究了食糜依赖性血管紧张素11的形成是否有助于SHR血压的调节。16周龄Wistar-Kyoto （WKY）大鼠的收缩压为113 +/- 9 mmHg，而SHR大鼠的收缩压为172 +/- 3 mmHg。采用合成底物测定血管紧张素转换酶（ACE）和酶切酶活性，发现SHR主动脉提取物的ACE和酶切酶活性显著高于WKY大鼠主动脉提取物。以血管紧张素I为底物，我们发现SHR中血管紧张素11的形成明显高于WKY大鼠，并且血管紧张素11的形成被ACE抑制剂完全抑制，而不被酶抑制剂抑制。在WKY大鼠和SHR大鼠主动脉提取物中均未检测到RVCH mRNA的表达。在从WKY大鼠和SHR分离的颈动脉中，ACE抑制剂完全抑制血管紧张素i诱导的血管收缩，而乳糜酶抑制剂则不能。在WKY大鼠和SHR中，Anglotensin i诱导的升压反应也被ACE抑制剂完全抑制，但它们不受乳糜酶抑制剂的影响。在SHR中，ACE抑制剂和血管紧张素11受体阻滞剂表现出同等的降压作用，但乳糜酶抑制剂没有降压作用。这些结果表明，在本研究中，食糜依赖性血管紧张素11没有调节SHR患者的血压。
Vascular smooth muscle cells in spontaneously hypertensive rats (SHR) express angiotensin II-forming chymase (rat vascular chymase [RVCH]), which may contribute to blood pressure regulation. In this study, we studied whether chymase-dependent angiotensin 11 formation contributes to the regulation of blood pressure in SHR. The systolic blood pressure in 16-week-old Wistar-Kyoto (WKY) rats was 113 +/- 9 mmHg, compared to 172 +/- 3 mmHg in SHR. Using synthetic substrates for measuring angiotensin-converting enzyme (ACE) and chymase activities, it was found that both ACE and chymase activities in extracts from SHR aortas were significantly higher than in those from WKY rat aortas. Using angiotensin I as a substrate, angiotensin 11 formation in SHR was found to be significantly higher than that in WKY rats, and its formation was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. RVCH mRNA expression could not be detected in aorta extracts from either WKY rats or SHR. In carotid arteries isolated from WKY rats and SHR, angiotensin I-induced vasoconstriction was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. Anglotensin I-induced pressor responses in both WKY rats and SHR were also completely inhibited by an ACE inhibitor, but they were not affected by a chymase inhibitor. In SHR, an ACE inhibitor and an angiotensin 11 receptor blocker showed equipotent hypotensive effects, but a chymase inhibitor did not have a hypotensive effect. These results indicated that chymase-dependent angiotensin 11 did not regulate blood pressure in SHR in the present study.