β‐ARs are coupled through G αs to adenylyl cyclases (AC) and the generation of cAMP, which in turn activates the cAMP‐dependent protein kinase (PKA). This “fight‐or‐flight” response is mediated primarily by noradrenaline and adrenaline acting on β‐adrenergic receptors (β‐ARs) at the surface of cardiac myocytes. The sympathetic nervous system is responsible for adaptation of cardiac output to stress and physical exercise.
A bolus injection of isoproterenol increased RV dP/dt max≈5‐fold versus 3‐fold in LV. Finally LV and RV intracavitary pressures were recorded in anesthetized beagle dogs. Both PDE3 and PDE4 contributed to the β‐AR regulation of cytoplasmic, and the difference between LVMs and RVMs was abolished by PDE3 inhibition and attenuated by PDE4 inhibition. Accordingly, β‐AR regulation of I Ca,L and I Ks were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was increased in RVMs. FRET imaging using targeted Epac2camps sensors revealed no change in subsarcolemmal, but a 2‐fold higher β‐AR stimulation of cytoplasmic in RVMs versus LVMs.
Isoproterenol increased sarcomere shortening ≈10‐fold and Ca 2+‐transient amplitude ≈2‐fold in LV midmyocytes (LVMs) versus ≈25‐fold and ≈3‐fold in RVMs. Intracellular and PKA activity were measured by live cell imaging using FRET‐based sensors. Sarcomere shortening, Ca 2+ transients, I Ca,L and I Ks currents were recorded in isolated dog LV and RV midmyocytes. Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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