Interventricular differences in β-adrenergic responses in the canine heart: Role of phosphodiesterases

Background: rv and lv have different embryologic,structural,metabolic,and electrophysiologic characteristics,but whether interventricular differences exist in β-adrenergic (β-ar) responsiveness is unknown. in this study,we examine whether β-ar response and signaling differ in right (rv) versus left (lv) ventricles. methods and results: sarcomere shortening,ca2+ transients,ica,l and iks currents were recorded in isolated dog lv and rv midmyocytes. intracellular [camp] and pka activity were measured by live cell imaging using fret-based sensors. isoproterenol increased sarcomere shortening ≈10-fold and ca2+-transient amplitude ≈2-fold in lv midmyocytes (lvms) versus ≈25-fold and ≈3-fold in rvms. fret imaging using targeted epac2camps sensors revealed no change in subsarcolemmal [camp],but a 2-fold higher β-ar stimulation of cytoplasmic [camp] in rvms versus lvms. accordingly,β-ar regulation of ica,l and iks were similar between lvms and rvms,whereas cytoplasmic pka activity was increased in rvms. both pde3 and pde4 contributed to the β-ar regulation of cytoplasmic [camp],and the difference between lvms and rvms was abolished by pde3 inhibition and attenuated by pde4 inhibition. finally lv and rv intracavitary pressures were recorded in anesthetized beagle dogs. a bolus injection of isoproterenol increased rv dp/dtmax≈5-fold versus 3-fold in lv. conclusion: canine rv and lv differ in their β-ar response due to intrinsic differences in myocyte β-ar downstream signaling. enhanced β-ar responsiveness of the rv results from higher camp elevation in the cytoplasm,due to a decreased degradation by pde3 and pde4 in the rv compared to the lv. © 2014 the authors.