In vivo characterization of the adrenergic receptors in the working canine heart.

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Abstract
The analysis of multiple indicator dilution data shows that the ratio of the interstitial space size available for tracer norepinephrine to that for sucrose is greater than 1. The space increment appears to be consequent to binding of tracer to sites in the interstitial space, so the hypothesis that these could be adrenergic receptors was examined. Following the injection of desmethylimipramine or tyramine to increase norepinephrine values, increases in heart rate and rate-pressure product correlated closely with decreases in the tracer norepinephrine:sucrose space ratio. Although capillary and interstitial norepinephrine values are ordinarily disparate, in the subset of experiments in which measured circulating plasma levels are close to equal in aorta and coronary sinus, the interstitial values will virtually equal plasma levels. In this group of experiments, the space ratio values can be related to interstitial norepinephrine values. The ratio diminished with increase in the levels of interstitial norepinephrine, apparently due to a progressively greater occupancy of adrenergic receptors by the endogenous norepinephrine and, at high levels of circulating norepinephrine, when there was intense cardiac sympathetic stimulation, the space ratio approached unity. Quantitative analysis of this behavior made it possible to obtain in vivo estimates of the equilibrium dissociation constant (0.64 mM) and the density or concentration of receptor sites (271 f[femto]mol/g). The dissociation constant lies in the physiological midrange of interstitial norepinephrine concentrations.

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