Summary
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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 (\t-)noradrenaline being simultaneously infused (0.2 gg kg\t-1 min\t-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 (C v) and arterial (C v) 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.
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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).
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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 C v/C a and pointed towards net removal of noradrenaline from the pulmonary circulation.
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4.
The fractional pulmonary extractions [1 - (C a/C a)] of the three types of 3H-noradrenaline did not differ from each other and were not affected by the simultaneous infusion of unlabelled noradrenaline. Moreover, the fractional pulmonary extraction of endogenous noradrenaline resembled that of infused 3H- and unlabelled noradrenaline, suggesting that there was little, if any, overflow of endogenous noradrenaline into plasma during passage through the pulmonary circulation.
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5.
From the clearance of noradrenaline from mixed central venous plasma, its fractional pulmonary extraction and the cardiac output of plasma estimates of the following steady-state kinetic parameters for infused noradrenaline were obtained: pulmonary, systemic as well as total body clearance (13.4, 67.9, 72.6 ml kg\t-1 min\t-1) and fractional extraction (0.128, 0.650, 0.695). The rates at which infused noradrenaline was eliminated from the pulmonary and systemic circulation amounted to 18.4 and 81.6% of the total body elimination rate, respectively.
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6.
The infusion of unlabelled noradrenaline increased plasma levels of 3,4-dihydroxyphenylglycol (DOPEG) by a factor of 1.2. DOPEG concentrations in arterial plasma were 4.9% higher than those in mixed central venous plasma. Hence, there was some net formation of DOPEG in the pulmonary circulation.
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This study was supported by the Deutsche Forschungsgemeinschaft (Gr 490/5). Some of the results were presented to the German Pharmacological Society (Halbrügge et al. 1988 a)
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Halbrügge, T., Ungell, AL., Wölfel, R. et al. Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 338, 361–367 (1988). https://doi.org/10.1007/BF00172110
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DOI: https://doi.org/10.1007/BF00172110