Birth and maturation are associated with dramatic alterations in blood flow regulation. One important modulator of blood flow is adenosine (ADO). However, little information exists about developmental changes in ADO modulation of blood flow. The central hypothesis of this investigation is that ADO modulation of coronary blood flow will change with development and the changes can be explained by cellular differences in ADO production and metabolism. To address this hypothesis we will accomplish the following: I.) Aims related to adenosine and local regulation of coronary flow.
Aim I A: Determine adenosine production during development.
Aim I B: Determine response to adenosine during development. II.) Aims related to cellular basis of developmental differences.
Aim II A: Determine ADO production by myocytes during development.
Aim II B: Determine ADO changes in cAMP and cGMP in vascular smooth muscle cells.
Aim II C: Determine uptake and transport of ADO in cardiac endothelial cells. Understanding the mechanisms of coronary flow regulation will provide new information about cardiac development and may provide information with clinical relevance to the management of premature infants and newborns with congenital heart disease.
