ABSTRACT

Cyclic nucleotides regulate a wide variety of processes in vascular smooth muscle cells (SMCs) from short-term action in smooth muscle relaxation to long-term processes such as gene expression and cell growth. Early studies using diethylamino ethanol (DEAE) ion exchange chromatography together with Phosphodiesterases (PDE) assays defined several distinct types of PDE activities present in smooth muscles from different vascular beds in various species including human, bovine, porcine, rabbit, and rat. A normal artery consists of quiescent arterial SMCs covered by a monolayer of endothelial cells lining the interior surface of the blood vessel. Endothelium-derived nitric oxide (NO) plays a critical role in attenuating SMC hyperplasia. Abnormal endothelial responses can lead to reduced bioavailability of NO. The role of PDE5 in NO/cyclic guanosine monophosphate (cGMP) signaling might be extended to other abnormal vascular features associated with changes in cGMP signaling due to endothelial dysfunction, such as SMC hyperplasia.