CONSTITUTIVE NONEXOCYTOTIC NOREPINEPHRINE RELEASE IN SYMPATHETIC-NERVES OF IN-SITU CANINE HEART

Nonexocytotic norepinephrine bulk overflow from sympathetic nerves has been previously demonstrated in the perfused isolated heart only afte r inhibition of sympathetic nerve metabolism by hypoxia, ischemia, or metabolic inhibitors. The measurement, however, ignores simultaneous u ptake of norepinephrine by sympathetic nerves. We quantitated simultan eous norepinephrine uptake and release in pentobarbital-anesthetized d ogs by the use of a transient tracer approach, the multiple indicator dilution technique, combined with measurement of endogenous arterial a nd venous plasma norepinephrine levels. Sympathetic vesicles were prev iously depleted by reserpine, and desipramine was used to inhibit the neuronal membrane pump. Labeled albumin, sucrose, and norepinephrine w ere injected into the coronary artery, and sequential samples were col lected from the coronary sinus. Reserpine pretreatment significantly d epleted tissue and decreased plasma norepinephrine levels; tracer nore pinephrine uptake increased slightly, and there was a substantial decr ease in the rate of release of unlabeled norepinephrine. Desipramine t hen decreased tracer uptake and virtually eliminated norepinephrine re lease. We conclude that desipramine-suppressible, constitutive nonexoc ytotic norepinephrine release is present in cardiac sympathetic nerves .