TY - JOUR
T1 - Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy
T2 - NO• and beyond
AU - Ritchie, Rebecca H.
AU - Irvine, Jennifer C.
AU - Rosenkranz, Anke C.
AU - Patel, Ruchi
AU - Wendt, Igor R.
AU - Horowitz, John D.
AU - Kemp-Harper, Barbara K.
N1 - Funding Information:
Dr. Ritchie is supported by grants from the National Health and Medical Research Council ( NHMRC ) of Australia ( ID472642 and ID526638 ) and the Diabetes Australia Research Trust, and is the recipient of a NHMRC Senior Research Fellowship ( ID472673 ). Prof Horowitz is supported by grants from the NHMRC ( ID418968 , ID472642 and ID565404 ). Dr. Kemp-Harper is a Foundation for High Blood Pressure Research Postdoctoral Fellow (Australia) and is supported by grants from the NHMRC ( ID491134 and ID472642 ).
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Cardiomyocyte
KW - Cyclic GMP
KW - Guanylyl cyclase
KW - Myocardium
KW - Natriuretic peptides
KW - Nitric oxide
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U2 - 10.1016/j.pharmthera.2009.08.001
DO - 10.1016/j.pharmthera.2009.08.001
M3 - Review article
C2 - 19723539
AN - SCOPUS:70449718779
SN - 0163-7258
VL - 124
SP - 279
EP - 300
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 3
ER -