Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit.
1. Rabbits were anaesthetized with urethane/chloralose and infused intravenously with trace amounts of 3H-2,5,6-, 3H-7,8- or 3H-7-(-)noradrenaline either without or with unlabelled (-)noradrenaline being simultaneously infused (0.2 micrograms kg-1 min-1). To obtain clearance values and extraction ratios for the pulmonary, systemic and total circulation, steady-state concentrations of infused noradrenaline were determined in mixed central venous (Cv) and arterial (Ca) plasma. Heart rate and blood pressure were recorded via the carotid artery, and the dye dilution method was used to determine the cardiac output of plasma. 2. The simultaneous infusion of unlabelled noradrenaline, which increased plasma levels of noradrenaline by a factor of 5, had no significant effect on either heart rate, blood pressure or cardiac output (when determined at steady state of the noradrenaline infusion). 3. The simultaneous infusion of unlabelled noradrenaline did not affect the clearance values of any of the three type of 3H-noradrenaline. Moreover, the clearances of the various types of 3H-noradrenaline were virtually identical and agreed with that of unlabelled noradrenaline. However, the clearance of labelled and unlabelled noradrenaline from arterial plasma was 1.15 times higher than that from central venous plasma. This factor corresponded to the ratio of Cv/Ca and pointed towards net removal of noradrenaline from the pulmonary circulation. 4. The fractional pulmonary extractions [1-(Ca/Cv)] of the three types of 3H-noradrenaline did not differ from each other and were not affected by the simultaneous infusion of unlabelled noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
Halbrügge
T
T
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Ungell
A L
AL
Wölfel
R
R
Graefe
K H
KH
D000758:Anesthesia; D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011817:Rabbits
D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine