Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation.
Coronary kinin generation mediates nitric oxide release after angiotensin receptor stimulation.
复制标题
血管紧张素受体刺激后，冠状激肽的产生介导一氧化氮的释放。
DOI：
10.1161/01.hyp.26.1.164
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Hintze,TH
中科院分区：
文献类型：
--
作者：
Seyedi,N;Xu,X;Nasjletti,A;Hintze,TH
我们的目标是确定血管紧张素II（Ang II）及其代谢片段是否释放一氧化氮，以及这种情况发生在犬心脏血管中的机制。我们将20毫克的微血管或大冠状动脉在磷酸盐缓冲盐水中孵育20分钟，并测量亚硝酸盐的释放。在10− 5 mol/L的Ang I、II、III、IV和Ang-（1-7）作用下，亚硝酸盐释放量分别从27±2增加到103±5、145± 1 - 7、84±4、107±16和54±4 pmol/mg（P<0.05）。N ω-硝基-L-精氨酸甲酯（100 μmol/L）可阻断血管紧张素的作用，表明亚硝酸盐是一氧化氮代谢的产物，而缓激肽B_2受体拮抗剂Hoe 140（10 μmol/L）可阻断血管紧张素的作用，表明其可能参与局部激肽的形成。蛋白酶抑制剂抑肽酶（10 μmol/L）和大豆胰蛋白酶抑制剂阻断局部激肽的形成，抑制所有血管紧张素释放亚硝酸盐。血管紧张素非选择性（saralasin），1型特异性（氯沙坦）和2型特异性（PD 123319）受体拮抗剂取消了响应于所有片段释放的亚硝酸盐。1型和2型血管紧张素及其受体介导Ang I、II、III和Ang-（1-7）后的亚硝酸盐释放，而只有2型受体介导Ang IV后的亚硝酸盐释放。在大冠状动脉中获得了类似的结果。总之，正常狗心脏中冠状微血管和大动脉对血管紧张素肽的反应中形成亚硝酸盐是由于冠状血管壁中局部激肽产生的激活。
Our goal was to determine whether angiotensin II (Ang II) and its metabolic fragments release nitric oxide and the mechanisms by which this occurs in blood vessels from the canine heart. We incubated 20 mg of microvessels or large coronary arteries in phosphate-buffered saline for 20 minutes and measured nitrite release. Nitrite release increased from 27±2 up to 103±5, 145±17, 84±4, 107±16, and 54±4 pmol/mg (P<.05) in response to 10−5mol/L of Ang I, II, III, IV, and Ang-(1-7), respectively. The effects of all angiotensins were blocked byNω-nitro-l-arginine methyl ester (100 μmol/L), indicating that nitrite was a product of nitric oxide metabolism, and by Hoe 140 (10 μmol/L), a specific bradykinin B2receptor antagonist, indicating a potential role for local kinin formation. The protease inhibitors aprotinin (10 μmol/L) and soybean trypsin inhibitor, which block local kinin formation, inhibited nitrite release by all of the angiotensins. Angiotensin nonselective (saralasin), type 1–specific (losartan), and type 2–specific (PD 123319) receptor antagonists abolished the nitrite released in response to all the fragments. Angiotensin type 1 and type 2 and receptors mediate nitrite release after Ang I, II, III, and Ang-(1-7), whereas only type 2 receptors mediate nitrite release after Ang IV. Similar results were obtained in large coronary arteries. In summary, formation of nitrite from coronary microvessels and large arteries in the normal dog heart in response to angiotensin peptides is due to the activation of local kinin production in the coronary vessel wall.