Journal
PHARMACOLOGY & THERAPEUTICS
Volume 122, Issue 3, Pages 216-238Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2009.02.009
Keywords
cGMP; Cardiovascular disease; Soluble guanylyl cyclase; Natriuretic peptide receptor; PKG; Phosphodiesterases
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Funding
- NHLBI NIH HHS [T32 HL007227, R01 HL089297, R01 HL089297-01A1, R01 HL089297-02, T32 HL007227-33] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007227, R01HL089297] Funding Source: NIH RePORTER
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Cyclic guanosine 3',5'-monophosphate (cGMP) mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular system. Dysfunctional signaling at any step of the cascade - cGMP synthesis, effector activation, or catabolism - have been implicated in numerous cardiovascular diseases, ranging from hypertension to atherosclerosis to cardiac hypertrophy and heart failure. In this review, we outline each step of the cGMP signaling cascade and discuss its regulation and physiologic effects within the cardiovascular system. In addition, we illustrate how cGMP signaling becomes dysregulated in specific cardiovascular disease states. The ubiquitous role cGMP plays in cardiac physiology and pathophysiology presents great opportunities for pharmacologic modulation of the cGMP signal in the treatment of cardiovascular diseases. We detail the various therapeutic interventional strategies that have been developed or are in development, summarizing relevant preclinical and clinical studies. (C) 2009 Elsevier Inc. All rights reserved.
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