Pulmonary hypertension (PH) is a disabling disease resulting from abnormalities in the pulmonary vascular bed. One aspect of pulmonary hypertension that is of interest is the remodeling of the vasculature which occurs in response to a hypoxic event. It has been shown that change occurs in smooth muscle cells as well as the endothelial cells, making them more proliferative and responsive to mitogenic agents. When this remodeling occurs the balance in between secreted mediators of vasoconstriction and vasodilation is disrupted The calcitonin gene-related peptide (CGRP) is a potent peptide vasodilator. It has been proposed to benefit pulmonary hypertension. An in vivo adenovirus mediated transfer of the gene encoding prepro-CGRP into mice with chronic hypoxia-induced pulmonary hypertension demonstrated its ability to alleviate the symptoms of PH and lower pulmonary arterial pressure. We hypothesize that overexpression of CGRP leads to the inhibition of vascular smooth muscle cell proliferation mediated through a cGMP/PKA pathway or cGMP/PKG mediated pathway. CGRP has also been shown to increase cAMP levels in certain preparations suggesting this nucleotide plays a role in the action of this peptide. The present study is aimed at delineating the mechanism by which the CGRP peptide acts and to propose a potential therapeutic application
