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 important limitation of NE spillover is that it reflects not only release but also uptake processes that intervene before the transmitter reaches the circulation. To overcome this limitation, we developed a method for estimating NE release based on measurements of the specific activities of [H-3]NE in plasma and interstitial fluid during intravenous infusion of [H-3]NE. We applied this method to examine relationships among NE release, tissue uptake, and spillover in the human heart, kidneys, and forearm. The sum of uptake and spillover of released NE provided an estimate of NE release into the interstitial fluid. In the kidneys, 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 organs, so that assessing regional sympathetic function requires an understanding of the relationship of NE spillover to NE release.