Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease.
Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease.
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DOI：
10.1016/j.phrs.2017.05.020
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发表时间：
2017-11
影响因子：
9.3
通讯作者：
Mullick AE
中科院分区：
文献类型：
--
作者：
Ferrario CM;Mullick AE
世纪的发现确立了肾素血管紧张素醛固酮系统通过自分泌、旁分泌和内分泌信号传导在维持血压、液体容量和电解质稳态中的重要性。虽然研究不断产生血管紧张素II和血管紧张素-（1-7）的新功能，但这些新发现的基础研究和临床应用之间的差距正在扩大。随着血管紧张素转化酶抑制剂和血管紧张素II受体阻滞剂作为治疗心血管和肾脏疾病的重要药物的疗效数据的积累，越来越明显的是，所实现的临床获益是次优的，并且令人惊讶地与其他治疗干预所能实现的获益没有什么不同。我们讨论了这个问题，并总结了新的途径和机制影响血管紧张素II的合成和行动。血管紧张素II产生的非肾素依赖性非经典途径的存在基本上不受抑制肾素血管紧张素系统活性的药物的影响。因此，新的努力应针对开发药物，可以有效地阻止细胞内血管紧张素II的合成和/或行动。改善药物对心脏或肾脏疾病部位的渗透，抑制糜蛋白酶-人类心脏中主要的血管紧张素II形成酶-和/或抑制血管紧张素原合成都将是抑制该系统的更有效策略。此外，考虑到血管紧张素II在维持肾稳态机制中的作用，任何新的抑制剂都应具有靶向致病性血管紧张素II信号传导过程的更大选择性，从而限制不适当的抑制。
A collective century of discoveries establishes the importance of the renin angiotensin aldosterone system in maintaining blood pressure, fluid volume and electrolyte homeostasis via autocrine, paracrine and endocrine signaling. While research continues to yield new functions of angiotensin II and angiotensin-(1-7), the gap between basic research and clinical application of these new findings is widening. As data accumulates on the efficacy of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers as drugs of fundamental importance in the treatment of cardiovascular and renal disorders, it is becoming apparent that the achieved clinical benefits is suboptimal and surprisingly no different than what can be achieved with other therapeutic interventions. We discuss this issue and summarize new pathways and mechanisms effecting the synthesis and actions of angiotensin II. The presence of renin-independent non-canonical pathways for angiotensin II production are largely unaffected by agents inhibiting renin angiotensin system activity. Hence, new efforts should be directed to develop drugs that can effectively block the synthesis and/or action of intracellular angiotensin II. Improved drug penetration into cardiac or renal sites of disease, inhibiting chymase –the primary angiotensin II forming enzyme in the human heart–, and/or inhibiting angiotensinogen synthesis would all be more effective strategies to inhibit the system. Additionally, given the role of angiotensin II in the maintenance of renal homeostatic mechanisms, any new inhibitor should possess greater selectivity of targeting pathogenic angiotensin II signaling processes and thereby limit inappropriate inhibition.
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DOI：
10.1177/1470320313515039
发表时间：
2015-12
期刊：
Journal of the renin-angiotensin-aldosterone system : JRAAS
影响因子：
--
作者：
Alzayadneh EM;Chappell MC
通讯作者：
Chappell MC
影响因子：
14.9
作者：
BOIZIAU, C;KURFURST, R;TOULME, JJ
通讯作者：
TOULME, JJ
影响因子：
3.7
作者：
Ahmad S;Simmons T;Varagic J;Moniwa N;Chappell MC;Ferrario CM
通讯作者：
Ferrario CM
DOI：
10.1152/ajpheart.01144.2010
发表时间：
2011-03-01
影响因子：
4.8
作者：
Arakawa, Hideki;Chitravanshi, Vineet C.;Sapru, Hreday N.
通讯作者：
Sapru, Hreday N.
影响因子：
2.7
作者：
Arakawa, Hideki;Kawabe, Kazumi;Sapru, Hreday N.
通讯作者：
Sapru, Hreday N.