3-adrenoceptors does not occur in the left ventricle that is exposed to the same elevated circulating norepinephrine (NE) as the right ventricle of the RHF animals, some local tissue factors must exist and play an important role in the chamber-specific fl-adrenoceptor downregulation in the failing right ventricle.' Similar findings were recently reported in humans with RHF secondary to primary pulmonary hypertension,5 confirming the importance of local rather than systemic mechanisms in

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... g the 1-receptor downregulation. Studies on adrenergic transmission6,7 have shown that the major mechanism responsible for removal of previously released NE into the interstitium and rapid termination of the effects of noradrenergic impulses in most organs involves active transport systems at the adrenergic nerve terminals that pump NE back to nerve terminals. Agents that inhibit the NE reuptake trans-by guest on July 21, 2018 http://circ.ahajournals.org/ Downloaded from by guest on July 21, 2018