Interstitial noradrenaline concentration of rat hearts as influenced by cellular catecholamine uptake mechanisms.
Marked concentration differences of noradrenaline (NA) between the vascular and the interstitial compartment were detected by sampling interstitial transudate from isolated perfused rat hearts. The ratios of vascular/interstitial concentration amounted to 7.4 to 1.3 depending on the concentration of NA administered (3 x 10(-9) to 10(-6) M). These concentration differences were abolished by inhibitors of uptake1 [desipramine (DMI)] and uptake2 (O-methyl-isoprenaline (OMI)). Neuronal uptake1 was characterized by a Km of 0.22 mumol/l and a Vmax of 370 pmol x min-1 x gWWT-1, extraneuronal uptake2 by a KUPTAKE of = 0.313 min-1. The apparent permeability surface area (P x S)-product calculated from uptake rate and transcapillary concentration difference was significantly decreased by administrating 100 mumol/l (NA) in presence of DMI. A presumed endothelial uptake mechanism contributing to catecholamine translocation was investigated in endothelial cells in culture. These cells showed a specific noradrenaline uptake with a K(m) of 4.35 mumol/l and a Vmax of about 75 pmol x min-1 x gWWT-1. Any inhibition by inhibitors of both of the two noradrenaline uptakes was lacking. The uptake rate of this mechanism is insufficient to contribute to the diffusive conductivity of the capillary wall (P x S-product). We conclude from our investigations on interstitial concentrations of catecholamines and transcapillary concentration differences, that the capillary wall, owing to its metabolic and diffusional characteristics, influences the exchange of catecholamines to a substantial and physiologically relevant extent.
Obst
O O
OO
Department Physiology, Medical Faculty Aachen, Germany.
Linssen
M C
MC
Van der Vusse
G J
GJ
Kammermeier
H
H
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003891:Desipramine; D009638:Norepinephrine