DIFFERENT RELATIONSHIPS OF SPILLOVER TO RELEASE OF NOREPINEPHRINE IN HUMAN HEART, KIDNEYS, AND FOREARM

Spillover of norepinephrine (NE) into plasma is used frequently as an index of NE release and therefore of sympathetic nerve activity. An im portant limitation of NE spillover is that it reflects not only releas e but also uptake processes that intervene before the transmitter reac hes the circulation. To overcome this limitation, we developed a metho d for estimating NE release based on measurements of the specific acti vities of [H-3]NE in plasma and interstitial fluid during intravenous infusion of [H-3]NE. We applied this method to examine relationships a mong NE release, tissue uptake, and spillover in the human heart, kidn eys, and forearm. The sum of uptake and spillover of released NE provi ded an estimate of NE release into the interstitial fluid. In the kidn eys, NE release averaged three times NE spillover, in skeletal muscle, 12 times NE spillover, and in the heart, >20 times NE spillover. Thus NE release greatly and variably exceeds NE spillover from these organ s, so that assessing regional sympathetic function requires an underst anding of the relationship of NE spillover to NE release.