NOREPINEPHRINE RELEASE IN THE HUMAN FOREARM - EFFECTS OF EPINEPHRINE

It has been postulated that delayed facilitation of norepinephrine rel ease by epinephrine is causally related to the development of hyperten sion. It has been proposed that a brief increase in epinephrine concen trations results in the uptake of epinephrine into the sympathetic ner ve terminal. Subsequent rerelease of epinephrine stimulates presynapti c beta-adrenergic receptors, resulting in a prolonged increase in plas ma norepinephrine (NE) concentrations, with amplified sympathetic resp onses and vasoconstriction. To determine whether such epinephrine-indu ced, delayed facilitation of NE release occurs in a vascular bed drain ing resistance vessels and, if it occurs, whether that facilitation di ffers in hypertension, we used a radioisotope dilution method to measu re unstimulated and isoproterenol-stimulated forearm NE spillover befo re, during, and after a 50 ng/min infusion of epinephrine for 30 minut es directly into the brachial artery. No delayed facilitatory effects of epinephrine on forearm NE spillover were observed in either 6 normo tensive (NT) or 8 borderline hypertensive (BHT) subjects (NT unstimula ted forearm NE spillover preepinephrine 1.79+/-0.41 ng/min versus post epinephrine 2.36+/-0.65 ng/min, P=.38; BHT preepinephrine 2.24+/-0.70 ng/min versus postepinephrine 1.93+/-0.46 ng/min, P=.51; NT isoprotere nol-stimulated forearm NE spillover preepinephrine 4.61+/-1.01 ng/min versus postepinephrine 4.4+/-0.98 ng/min, P=.9; BHT Preepinephrine 4.0 4+/-1.36 ng/min versus postepinephrine 4.69+/-1.49 ng/min P=.5). We co nclude that the short-term local infusion of epinephrine does not have a delayed facilitatory effect on forearm NE spillover in NT or BHT su bjects. Therefore, the prolonged increase in NE concentrations after e pinephrine infusion previously shown systemically, and not seen locall y in the forearm, suggests that the delayed facilitatory response to e pinephrine may occur in other organs.