End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

作     者：Matthias Lohn Oliver Plettenburg Aimo Kannt Markus Kohlmann Armin Hofmeister Dieter Kadereit Peter Monecke Alexander Schiffer Anke Schulte Hartmut Ruetten Yuri Ivashchenko 

作者机构：Translational MedicineSanofi-AventisIndustriepark Hoechst65926 Frankfurt am MainGermany 

出 版 物：《World Journal of Cardiology》 (世界心脏病学杂志（英文版）（电子版）)

年 卷 期：2015年第7卷第1期

页      面：31-42页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Hypertension End organ damage Rhokinase Angiotensin converting enzyme-inhibition 

摘      要：AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.