Cardiac Uses of Phosphodiesterase-5 Inhibitors

Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017-2395, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 01/2012; 59(1):9-15. DOI: 10.1016/j.jacc.2011.07.051
Source: PubMed


Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases.

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Available from: Vera J Stecher, Aug 19, 2014
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    ABSTRACT: Phosphodiesterase type 5 (PDE5) is an enzyme that belongs to a large family of cyclic nucleotide PDEs that catalyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). cAMP and cGMP are two essential intracellular second messengers regulating many different cellular functions of living cells. PDE5 specifically breaks down the substrate cGMP. Inhibition of PDE5 increases intracellular cGMP levels by inhibiting its degradation. Sildenafil (Viagra) is a potent and selective inhibitor of cGMP-specific PDE5, and is the first oral treatment for males with erectile dysfunction, which was approved by Food and Drug Administration on March 27, 1998. Sildenafil binds to the catalytic site of PDE5 and inhibits the degradation of intracellular cGMP in smooth muscle within the corpus cavernosum, resulting in increased levels of cGMP that causes smooth muscle cell relaxation, vasodilation, and improves erectile function(1,2). (SELECT FULL TEXT TO CONTINUE).
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