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Advances in Heart Failure

Clinical Use of Phosphodiesterase-5 Inhibitors in Chronic Heart Failure

Marco Guazzi, MD, PhD

From the Heart Failure Unit, Cardiopulmonary Laboratory, Department of Medicine and Surgery, San Paolo Hospital, University of Milano, Italy.

Correspondence to Marco Guazzi, MD, PhD, FACC, Heart Failure Unit, Cardiopulmonary Laboratory, University of Milano, San Paolo Hospital, Via A. di Rudinì, 8, 20142 Milano, Italy. E-mail marco.guazzi@unimi.it

Received June 25, 2008; accepted September 16, 2008.

Key Words: heart failure • pharmacology

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Nowadays, the inhibitors of the phosphodiesterase enzyme type 5 (PDE5), thanks to a sustained relaxant activity on smooth muscles of the corpus cavernosum, are a widely used remedy for erectile dysfunction in man. This class of compounds was originally developed for the treatment of angina pectoris, based on the ability of oversignaling the pathway originated from nitric oxide (NO) and pursued via cGMP signaling. Because the clinical effects were not as promising as initially reported by experimental studies, PDE5 inhibitors¹ were not regarded as a remarkable advancement over commonly used nitrates. Subsequently, however, it was realized that the clinical applicability of the enhanced NO/cGMP pathway by inhibiting the PDE5 activity could be larger than previously thought. Over the last few years, the use of PDE5 inhibitors has been expanded to the therapeutic management of other cardiovascular disorders, including chronic heart failure (CHF). Their clinical applicability to CHF is the subject of this review.

	Phosphodiesterases

 
The homeostatic role of phosphodiesterases (PDEs) as related to the intracellular levels of cAMP and cGMP was first described by Sutherland,² who, because of this, was awarded the Nobel Prize for Physiology and Medicine in 1971. These enzymes hydrolyze the phosphodiester bond of cAMP and cGMP to form the inactive 5'-AMP and 5'-GMP. In optimizing the intracellular levels of cAMP and cGMP, breakdown is predominant over synthesis. PDEs comprise a superfamily with 11 subfamilies, which have been characterized on the basis of amino acid sequence, substrate specificity, pharmacological properties and allosteric regulation. Within these families, more than . . . [Full Text of this Article]