Labeled catecholamine uptake in the dog heart. Interactions between capillary wall and sympathetic nerve uptake.

Abstract

The kinetics underlying the uptake of tracer amounts of norepinephrine and isoproterenol by the heart were studied in a pentobarbital-anesthetized dog with the multiple indicator dilution technique. The circumflex coronary artery was perfused with blood from the femoral artery with a pressure-dependent system. A small bolus containing labeled albumin (a tracer confined to the vascular space), labeled sucrose (which penetrates into the extracellular space in a barrier-limited fashion) and labeled norepinephrine or isoproterenol was injected into the artery and outflow dilution curves were obtained from the coronary sinus. The myocardial capillary permeability for norepinephrine or isoproterenol, and their rate constants for uptake by the interstitial sympathetic fibers were assessed; the process is essentially unidirectional over the time of a single passage, because of the highly concentrative nature of the uptake. A major resistance to catecholamine transfer was found at the capillary surface (approximately half of the label emerged at the outflow without leaving the circulation) and a neuronal uptake process occurred beyond the barrier large enough that, after steady infusion, it would be expected to reduce the tracer concentration of norepinephrine to a value 1/6 that in the plasma space. The injection of desmethylimipramine selectively diminished the apparently unidirectional flux of labeled norepinephrine into the neuronal terminals; this uptake was significantly lower for isoproterenol than for norepinephrine. The capillary-interstitium-concentrative uptake mechanism partially explains the quantitatively different cardiac responses to infused and locally released catecholamines.