Section Review Cardiovascular & Renal: Phosphodiesterase 5 inhibitors in development for cardiovascular therapy

Abstract

Phosphodiesterase 5 (PDE 5), which is actually a family of PDE isozymes, hydrolyses cGMP with a high degree of selectivity and is insensitive to calmodulin (CaM). PDE 5 has been identified in the aorta, mesenteric or pulmonary arteries and saphenous vein, suggesting that it plays an important role in the regulation of cGMP levels in vascular smooth muscle, much like stimulators of cGMP synthesis, such as endothelium-derived relaxing factor (EDRF) and atrial natriuretic peptide (ANP). Several selective and potent PDE 5 inhibitors, which can be used to determine the pharmacological effects on cardiovascular diseases, have been synthesised by various pharmaceutical companies and are currently being studied. Results have shown that these PDE 5 inhibitors dilate the large epicardial coronary artery in conscious pigs and selectively lower the pulmonary arterial pressure in animal models of congestive heart failure or pulmonary hypertension, suggesting that these inhibitors may be useful as a therapy for heart failure, pulmonary hypertension, and angina. It is likely that the therapeutic benefit of PDE 5 inhibitors will be assessed in the near future.

Key Words:

• angina
• cardiovascular disease
• cyclic GMP
• heart failure
• hypertension
• phosphodiesterase 5 inhibitor
• pulmonary hypertension