Banegas Inmaculada, Prieto Isabel, Vives Francisco, Alba Francisco, de Gasparo Marc, Segarra Ana Belen, Hermoso Francisco, Durán Raquel, Ramírez Manuel
Unit of Physiology, University of Jaén, Spain.
J Renin Angiotensin Aldosterone Syst. 2006 Sep;7(3):129-34. doi: 10.3317/jraas.2006.021.
The brain aminopeptidases that participate in the enzymatic cascade of the renin-angiotensin system play a major role in blood pressure (BP) control, and their study offers new perspectives for the understanding of central BP control and the treatment of hypertension. In this system, angiotensin II is converted to angiotensin III (Ang III) by glutamyl aminopeptidase (GluAP) and Ang III is further metabolised to angiotensin IV by alanyl aminopeptidase or arginine-aminopeptidase. It is now clear that Ang III is the key active form of the central angiotensins, exerting tonic stimulatory control over BP. Therefore, the development of GluAP inhibitors as potential antihypertensive agents offers new perspectives for therapy. Brain aspartyl aminopeptidase, which converts angiotensin I to angiotensin 2-10, is also a possible target for antihypertensive therapy because of its potential role in BP control. Finally, since changes in BP levels, that paralleled changes in brain and plasma aminopeptidase activities, were observed after unilateral lesions of the nigrostriatal system, brain asymmetry, aminopeptidase activities and BP control appear to be related, resulting their interplay in an asymmetrical neuroendocrine response that differentially affect BP control. The study of this interaction may contribute to our understanding of how the brain controls BP.
参与肾素-血管紧张素系统酶促级联反应的脑氨肽酶在血压控制中起主要作用，对其研究为理解中枢血压控制和高血压治疗提供了新视角。在该系统中，血管紧张素II通过谷氨酰氨肽酶（GluAP）转化为血管紧张素III（Ang III），Ang III再通过丙氨酰氨肽酶或精氨酸氨肽酶进一步代谢为血管紧张素IV。现在已经明确，Ang III是中枢血管紧张素的关键活性形式，对血压发挥持续性刺激控制作用。因此，开发GluAP抑制剂作为潜在的抗高血压药物为治疗提供了新视角。脑天冬氨酰氨肽酶可将血管紧张素I转化为血管紧张素2-10，因其在血压控制中的潜在作用，它也是抗高血压治疗的一个可能靶点。最后，由于在黑质纹状体系统单侧损伤后观察到血压水平的变化与脑和血浆氨肽酶活性的变化平行，脑不对称性、氨肽酶活性和血压控制似乎相关，导致它们在不对称神经内分泌反应中相互作用，对血压控制产生不同影响。对这种相互作用的研究可能有助于我们理解大脑如何控制血压。
