Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice -: A comparative study
Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice -: A comparative study
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DOI：
10.1016/j.peptides.2005.03.026
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发表时间：
2005-08-01
期刊：
影响因子：
3
通讯作者：
Gobeil, F
中科院分区：
文献类型：
--
作者：
Blais, PA;Côté, J;Gobeil, F
血加压素是Rioli等人新近报道的一种来源于血红蛋白a链的新型血管活性多肽。[Rioli V，Gozzo FC，Heimann As，Linardi A，Krieger Je，Shida CS，等.内肽酶24.15、神经溶素和血管紧张素转换酶的新型天然多肽底物。J Biol Chem 2003；278(10)：8547-55]。在麻醉的雄性Wistar大鼠中，这种多肽在静脉注射时表现出与缓激肽(BK)相似的降压作用，并被发现在体外和体内都被几种多肽酶代谢，包括血管紧张素转换酶(ACE)。在这项研究中，通过检测：(I)从兔肺中提纯的ACE孵育后的降解动力学和(Ii)静脉注射HP和BK的降压作用，对这些发现进行了扩展。或动脉内(i.a.)在雄性兔子、大鼠和小鼠身上。我们的研究结果表明，在体外，HP和BK都被ACE降解，但降解速度不同。此外，HP和BK在所有受试动物中都引起了一过性低血压，尽管在等摩尔基础上，HP相对于给药部位的反应明显低于BK(10-100倍)。在兔体内，静脉注射HP(10-100nmol/kg)引起的血压下降没有差别。或i.a.，提示没有肺/心脏失活，而不是BK(0.1-1nmol/kg)。B-2受体拮抗剂HoE-140(0.1mU/kg)和卡托普利(100 mU/kg)对细菌脂多糖(LPS)免疫增强Hp的体内效应无明显影响，但与BK相反。因此，HP作为一种微弱的降压介质，不激活激动素B-2受体，但使用一个功能部位和/或信号通路，似乎被内毒素上调。(C)2005 Elsevier Inc.保留所有权利。
Hemopressin is a novel vasoactive nonapeptide derived from hemoglobin's a-chain as recently reported by Rioli et al. [Rioli V, Gozzo FC, Heimann AS, Linardi A, Krieger JE, Shida CS, et al. Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. J Biol Chem 2003;278(10):8547-55]. In anesthetized male Wistar rats, this peptide exhibited hypotensive actions similar to those of bradykinin (BK) when administered intravenously (i.v.), and was found to be metabolized both in vitro and in vivo by several peptidases, including the angiotensin-converting enzyme (ACE). In this study, these findings were expanded upon by examining: (i) the degradation kinetics following incubation with ACE purified from rabbit lung and (ii) the blood pressure lowering effects of HP and BK injected i.v. or intra-arterially (i.a.) in male rabbits, rats, and mice. Our findings demonstrate that, in vitro, HP and BK are both degraded by ACE, but at different velocity rates. Furthermore, both HP and BK induced transient hypotension in all animals tested, although the responses to HP relative to the administration sites were significantly lower (by 10-100-fold) on an equimolar basis compared to those of BK. In rabbits, the decrease of blood pressure induced by HP (10-100 nmol/kg) did not differ whether it was administered i.v. or i.a., suggesting an absence of pulmonary/cardiac inactivation in contrast to BK (0.1-1 nmol/kg). The in vivo effect of HP was significantly potentiated in rabbits immunostimulated with bacterial lipopolysaccharide (LPS), but was unaffected by both the B-2 receptor antagonist HOE 140 (0.1 mu mol/kg) and captopril (100 mu g/kg), contrary to BK. Therefore, HP acts as a weak hypotensive mediator, which does not activate kinin B-2 receptors, but uses a functional site and/or signaling paths appearing to be up-regulated by LPS. (c) 2005 Elsevier Inc. All rights reserved.