State-of-the-Art Paper
Cyclic Guanosine Monophosphate Signaling and Phosphodiesterase-5 Inhibitors in Cardioprotection

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Cyclic guanosine monophosphate (cGMP) is an important intracellular second messenger that mediates multiple tissue and cellular responses. The cGMP pathway is a key element in the pathophysiology of the heart and its modulation by drugs such as phosphodiesterase (PDE)-5 inhibitors and guanylate cyclase activators may represent a promising therapeutic approach for acute myocardial infarction, cardiac hypertrophy, heart failure, and doxorubicin cardiotoxicity in patients. In addition, PDE-5 inhibitors may prove to be innovative therapeutic agents for enhancing the chemosensitivity of doxorubicin while providing concurrent cardiac benefit.

Key Words

cGMP
cardiomyocytes
infarction
ischemia
signaling

Abbreviations and Acronyms

ANP
atrial natriuretic peptide
BNP
B-type natriuretic peptide
cAMP
cyclic adenosine monophosphate
cGMP
cyclic guanosine monophosphate
DOX
doxorubicin
DMD
Duchenne muscular dystrophy
GC
guanylyl cyclase
I/R
ischemia-reperfusion
mdx
dystrophin-deficient
MI
myocardial infarction
mitoKATP
mitochondrial KATP
NO
nitric oxide
NOS
nitric oxide synthase
NP
natriuretic peptide
PDE
phosphodiesterase
pGC
particulate guanylyl cyclase
PKG
cyclic guanosine monophosphate–dependent protein kinases
sGC
soluble guanylyl cyclase

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This study was supported by grants from the National Institutes of Health (HL51045, HL79424, and HL93685) to Dr. Kukreja and a National Scientist Development Grant from the American Heart Association (10SDG3770011) to Dr. Salloum. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.