EFFECTS OF CONVERTING-ENZYME INHIBITORS ON ANGIOTENSIN AND BRADYKININ PEPTIDES
EFFECTS OF CONVERTING-ENZYME INHIBITORS ON ANGIOTENSIN AND BRADYKININ PEPTIDES
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DOI：
10.1161/01.hyp.23.4.439
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发表时间：
1994-04-01
期刊：
影响因子：
8.3
通讯作者：
DUNCAN, AM
中科院分区：
文献类型：
--
作者：
CAMPBELL, DJ;KLADIS, A;DUNCAN, AM
我们通过给大鼠饮用培哚普利或赖诺普利7天，检测血管紧张素转换酶抑制剂对血管紧张素和缓激肽循环和组织水平的剂量相关效应。0.006 mg/kg/天培哚普利组血浆血管紧张素II（Ang II）与Ang I的比值降低，0.017 mg/kg/天培哚普利组血浆肾素和Ang I升高。血浆Ang II水平直到1.4 mg/kg/天培哚普利才降低，在该剂量下血浆Ang I水平达到约25倍增加的平台。培哚普利对心脏、肺、主动脉和棕色脂肪组织中Ang II和Ang I水平的影响与血浆中观察到的结果平行。相比之下，肾血管紧张素I水平没有增加，肾血管紧张素II水平下降了40%，0.017毫克/公斤/天，相同的阈值，血浆肾素增加。培哚普利使循环缓激肽-（1-9）水平增加约8倍，阈值剂量为0.052 mg/kg/天，肾脏、心脏和肺中缓激肽-（1-9）水平增加，与血浆中观察到的变化平行。相比之下，主动脉和棕色脂肪组织缓激肽-（1-9）和缓激肽-（1-7）水平在培哚普利剂量低至0.006 mg/kg/天时增加数倍。当剂量低于Ang II/Ang I比值降低的阈值时，赖诺普利也可增加主动脉缓激肽-（1-9）和缓激肽-（1-7）水平。这些数据表明，肾血管紧张素Ⅱ水平和血管缓激肽-（1-9）水平响应于低剂量的转换酶抑制剂，并可能是这些化合物的作用的重要介质。在抑制剂剂量低于抑制Ang I转化的阈值时，主动脉和棕色脂肪组织中缓激肽-（1-9）和缓激肽-（1-7）水平平行增加，可能是由于与抑制“经典”不同的机制引起的。”血管紧张素转换酶。
We examined the dose-related effects of angioten- sin-converting enzyme inhibitors on circulating and tissue levels of angiotensin and bradykinin peptides by administering perindopril or lisinopril to rats in drinking water for 7 days. A reduction in the ratio of plasma angiotensin II (Ang II) to Ang I was seen for 0.006 mg/kg per day perindopril, with an increase in plasma renin and Ang I at 0.017 mg/kg per day. Plasma Ang II levels did not decrease until 1.4 mg/kg per day perindopril, at which dose plasma Ang I levels reached a plateau of an approximate 25-fold increase. The effects of perindopril on Ang II and Ang I levels in heart, lung, aorta, and brown adipose tissue were parallel to those observed for plasma. By contrast, renal Ang I levels did not increase, and renal Ang II levels decreased by 40% at 0.017 mg/kg per day, the same threshold seen for the increase in plasma renin. Perindopril increased circulating bradykinin-(1-9) levels approximately eightfold, with a threshold dose of 0.052 mg/kg per day, and increased bradykinin-(1-9) levels in kidney, heart, and lung in parallel with the changes observed for plasma. By contrast, aortic and brown adipose tissue bradykinin-(1-9) and bradykinin-(1-7) levels increased severalfold for perindopril doses as low as 0.006 mg/kg per day. Lisinopril also increased aortic bradykinin-(1-9) and bradykinin-(1-7) levels at doses below the threshold for the decrease in the ratio of Ang II to Ang I. These data indicate that renal Ang II levels and vascular bradykinin-(1-9) levels respond to low doses of converting enzyme inhibitor and may be important mediators of the effects of these compounds. The parallel increases in bradykinin-(1-9) and bradykinin-(1-7) levels in aorta and brown adipose tissue, at inhibitor doses below the threshold for inhibition of Ang I conversion, may result from a mechanism different from inhibition of ''classic'' angiotensin-converting enzyme.