The pulmonary vascular response to severe hypoxia is characterized by initial vasoconstriction followed by vasodilation. This hypoxic pulmonary vasodilation (HPVD) is not due to a failure of the contractile apparatus. The purpose of this proposal is to determine the transduction processes responsible for HPVD. These studies will test the hypothesis that HPVD occurs because of activation of smooth muscle or endothelial ATP-dependent potassium (KATP) channels due to either a fall in [ATP], or adenosine- induced stimulation of a Gi-protein. Studies will be performed to confirm that HPVD is due to KATP channel activation, determine whether adenosine mediates HPVD via a G-protein dependent mechanism, determine if a fall in [ATP] activates KATP channels and if this can be prevented with high glucose, and determine the relative contributions of vascular smooth muscle and endothelium on HPVD.
