ABSTRACT
The pulmonary vascular bed is a low-pressure system with a resistance approximately one-tenth that of systemic circulation. Phosphodiesterase 5 (PDE5) has been shown to be the main enzyme regulating cyclic guanosine monophosphate (cGMP) hydrolysis and downstream signaling in human pulmonary artery smooth muscle cells. PDE3 consists of two isoforms, termed PDE3A and PDE3B, which display distinct N-terminal domains that might confer differential subcellular localization of each isoform. The human PDE5A promoter overlaps with the A1-specific exon whereas the PDE5A2 promoter is located between the A3- and A2-specific exons. The clinical efficacy of PDE5 inhibitors suggests that there is considerable therapeutic potential for treatment of pulmonary arterial hypertension, and that these drugs may in fact target one of the contributory factors to the disease. The PDE5 inhibitor, sildenafil, was effective in relaxing phenylephrine-, serotonin-, and endothelin-1-induced contraction of main branch pulmonary vessels from normoxic-treated animals.
