Evidence for the role of angiotensin II biosynthesis in the rat internal anal sphincter tone
Evidence for the role of angiotensin II biosynthesis in the rat internal anal sphincter tone
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DOI：
10.1053/j.gastro.2004.03.056
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发表时间：
2004-07-01
期刊：
影响因子：
29.4
通讯作者：
Rattan, S
中科院分区：
文献类型：
--
作者：
De Godoy, MAF;Dunn, S;Rattan, S
背景与目的：肛门内括约肌张力对肛门直肠吻合术是重要的。本研究探讨了血管紧张素II作为肛门内括约肌肌源性张力的神经体液信号的作用。研究方法：我们确定了血管紧张素I，II，III和IV和血管紧张素-（1-7）对大鼠肛门内括约肌平滑肌的基础张力之前和之后的选择性受体拮抗剂和生物合成抑制剂的影响。使用的选择性药理学工具是氯沙坦（用于AT（1）受体）、PD 123，319（用于AT（2））、A-779 [用于血管紧张素-（1-7）]、卡托普利（用于血管紧张素转换酶）和amastatin（用于氨肽酶A和N）。采用高效液相色谱/紫外法测定血管紧张素。蛋白质印迹法测定AT（1）和AT（2）受体、ACE和氨肽酶A和N。结果：血管紧张素I、II和III通过AT（2）受体介导的浓度依赖性收缩肛门内括约肌。然而，在较高浓度下（100 nM至10 μ M），血管紧张素II通过AT（2）受体显示出抑制作用。卡托普利（1 μ M）抑制肛门内括约肌血管紧张素II的生物合成，拮抗血管紧张素I的收缩作用，重要的是，引起基础张力下降。Amastatin抑制血管紧张素II的作用，同时增强血管紧张素III的作用。相比之下，血管紧张素-（1-7）和血管紧张素IV只有轻微的影响，在肛门内括约肌。血管紧张素I、II和III;血管紧张素转换酶;氨肽酶A和氨肽酶N; AT（1）和AT（2）受体被证明存在于肛门内括约肌中。结论：局部产生的血管紧张素II可部分调节肛门内括约肌的基础张力。
Background & Aims: The internal anal sphincter tone is important for anorectal continence. This study examined the role of angiotensin II as a neurohumoral signal for the myogenic tone in the internal anal sphincter. Methods: We determined the effect of angiotensin I, II, III, and IV and angiotensin-(1-7) on the basal tone of the rat internal anal sphincter smooth muscle before and after selective receptor antagonists and biosynthesis inhibitors. Selective pharmacological tools used were losartan (for the AT(1) receptor), PD123,319 (for AT(2)), A-779 [for angiotensin-(1-7)], captopril (for angiotensin-converting enzyme), and amastatin (for aminopeptidases A and N). Angiotensins were measured by using high-performance liquid chromatography/UV. Western blot studies were used to determine AT(1) and AT(2) receptors, ACE, and aminopeptidases A and N. Results: Angiotensin I, II, and III produced concentration-dependent contraction in the internal anal sphincter mediated by AT(2) receptors. However, in the higher concentrations (from 100 nM to 10 muM), anglotensin II showed an inhibitory effect via AT(2) receptors. Captopril (1 muM) inhibited the biosynthesis of angiotensin II in the internal anal sphincter, antagonized the contractile effects of anglotensin I, and, importantly, caused a decrease in the basal tone. Amastatin inhibited the effects of anglotensin II while augmenting those of angiotensin III. In contrast, angiotensin-(1-7) and angiotensin IV had only minor effects in the internal anal sphincter. Angiotensin I, II, and III; angiotensin-converting enzyme; aminopeptidase A and aminopeptidase N; AT(1); and AT(2) receptors were shown to be present in the internal anal sphincter. Conclusions: Locally produced angiotensin II may partially regulate basal tone in the internal anal sphincter.