Phosphodiesterase 5 Inhibition to Treat Essential Hypertension

Abstract

Treatment of hypertension is a challenging task in cardiovascular medicine. The obviously simple concept that blood pressure (BP) must be “normalized” faces the intrinsic difficulty to decrease BP values, because the effectiveness of available drug classes in terms of BP reduction is in many cases not adequate to reach the therapeutic targets.1 One possible means of overcoming this limitation is to combine drugs with different mechanisms of action to obtain a synergistic effect on BP reduction.1 The more drug classes that are available, the more possibilities we have to obtain an effective BP control. The article from Oliver et al2 published in this issue of Hypertension represents the first study performed with an accurate experimental design and methodology demonstrating that inhibitors of isoform 5 of phosphodiesterase (PDE) might be potentially used as a new drug class for the treatment of essential hypertension. PDE is a family of isoenzymes with various tissue and cellular distribution and linkage to specific cGMP- and cAMP-dependent pathways3 (Figure). To date, ≥11 PDE isoforms have been identified, and their tissue distribution together with the availability of specific antagonists is the basis for a potential clinical use of PDE inhibitors.3 PDE 5, a cGMP-hydrolyzing isoform, is highly expressed in vascular smooth muscle cells of the corpora cavernosa, but it is also well represented in various other tissues, including peripheral, coronary, and pulmonary vessels. Sildenafil is a specific inhibitor of PDE 5 isoform and, therefore, increases intracellular cGMP concentration by inhibiting its breakdown with the consequence of potentiating the cGMP-mediated reduction of intracellular calcium concentration3 (Figure). This effect is clinically useful in patients with erectile dysfunction, characterized …