Randy S. Sprague and Madelyn Stumpf
The invention is directed to methods for controlling vascular tension in extremities to improve blood flow at extremities and control pulmonary blood pressure. More specifically, the invention is directed to the control of ATP release by red blood cells, via manipulating phosphodiesterase 3 in red blood cells using inhibitors of phosphodiesterase 3. The invention discloses (a) the mechanism by which RBCs can release ATP, (b) compositions to enhance the production of ATP by RBCs, and (c) methods of treating diseases such as pulmonary hypertension and diabetic blood flow problems. The inventors have defined a signal transduction pathway that relates physiological and pharmacological stimuli to ATP release from erythrocytes. This pathway includes the heterotrimeric G proteins Gi and Gs, adenylyl cyclase (AC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and the cystic fibrosis transmembrane conductance regulator (CFTR). It is important to note that, in this pathway, activation of either Gs or Gi results in the stimulation of AC activity and cAMP synthesis.