Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy: NO• and beyond

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• 作者：Rebecca H. Ritchie ; Jennifer C. Irvine ; Anke C. Rosenkranz ; Ruchi Patel ; Igor R. Wendt ; John D. Horowitz ; Barbara K. Kemp-Harper
• 关键词：Cardiomyocyte ; Cyclic GMP ; Guanylyl cyclase ; Myocardium ; Nitric oxide ; Natriuretic peptides
• 刊名：Pharmacology and Therapeutics
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：124
• 期：3
• 页码：279-300
• 全文大小：627 K

文摘

Left ventricular hypertrophy (LVH), an increased left ventricular (LV) mass, is common to many cardiovascular disorders, initially developing as an adaptive response to maintain myocardial function. In the longer term, this LV remodelling becomes maladaptive, with progressive decline in LV contractility and diastolic function. Indeed LVH is recognised as an important blood-pressure independent predictor of cardiovascular morbidity and mortality. The clinical efficacy of current treatments for LVH is reduced, however, by their tendency to slow disease progression rather than induce its reversal, and thus the development of new therapies for LVH is paramount. The signalling molecule cyclic guanosine-3′,5′-monophosphate (cGMP), well-recognised for its role in regulating vascular tone, is now being increasingly identified as an important anti-hypertrophic mediator. This review is focused on the various means by which cGMP can be stimulated in the heart, such as via the natriuretic peptides, to exert anti-hypertrophic actions. In particular we address the limitations of traditional nitric oxide (NO•) donors in the face of the potential therapeutic advantages offered by novel alternatives; NO• siblings, ligands of the cGMP-generating enzymes, soluble (sGC) and particulate guanylyl cyclases (pGC), and phosphodiesterase inhibitors. Further impact of cGMP within the cardiovascular system is also discussed with a view to representing cGMP-based therapies as innovative pharmacotherapy, alone or concurrent with standard care, for the management of LVH.