TY - JOUR
T1 - Effect of chlorphentermine on the pulmonary disposition of norepinephrine in the isolated perfused rabbit lung
AU - Angevine, Linda S.
AU - Nabeshima, Toshitaka
AU - Ho, Ing K.
AU - Mehendale, Harihara M.
N1 - Funding Information:
*These investigations were aided in part by a grant from the Mississippi Heart Association Research and Medical Education Fund and PHS grant from National Heart, Lung and Blood Institute, HL20622. Preliminary results of these studies were presented at the 19th Annual Meetings of the Society of Toxicology in Washington, D.C., March, 1980 (Toxic01 Appl Pharmacol Abst #138, A46, 1980). tPredoctora1 Trainee supported by a Toxicology Training Grant ES-07045. :Visiting faculty from Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Mei jo University, Tempakn-ku, Nagoya 468, Japan.
PY - 1981
Y1 - 1981
N2 - Cblorphentermine (CP) has been noted to cause primary pulmonary hypertension both clinically and experimentally. It was postulated that CP might affect the pulmonary clearance of endogenous vasoactive substances such as norepinephrine (NE). The uptake and metabolism of 14C-NE were followed in artificially ventilated isolated perfused rabbit lung preparations using a constituted perfusate with initial NE concentrations of 5 μg/100 ml. Perfusate samples were analyzed for total radioactivity, metabolites, and parent compound. Preloading the lungs with 0.25 mM CP significantly increased the concentration of total radioactivity, deaminated products, and decreased the concentration of normetanephrine in the perfusate. In addition, the accumulation of total radioactivity in the lung tissue after 60 min of perfusion was significantly decreased in CP-treated lungs. The proportion of deaminated metabolites in the lung tissue was slightly decreased while the percent of normetanephrine, and parent compound were significantly increased by the CP treatment. CP (0.1 mM) also inhibited the in vitro metabolism of NE by 79%. These results provide experimental evidence in support of a hindered pulmonary clearance of circulating NE by CP.
AB - Cblorphentermine (CP) has been noted to cause primary pulmonary hypertension both clinically and experimentally. It was postulated that CP might affect the pulmonary clearance of endogenous vasoactive substances such as norepinephrine (NE). The uptake and metabolism of 14C-NE were followed in artificially ventilated isolated perfused rabbit lung preparations using a constituted perfusate with initial NE concentrations of 5 μg/100 ml. Perfusate samples were analyzed for total radioactivity, metabolites, and parent compound. Preloading the lungs with 0.25 mM CP significantly increased the concentration of total radioactivity, deaminated products, and decreased the concentration of normetanephrine in the perfusate. In addition, the accumulation of total radioactivity in the lung tissue after 60 min of perfusion was significantly decreased in CP-treated lungs. The proportion of deaminated metabolites in the lung tissue was slightly decreased while the percent of normetanephrine, and parent compound were significantly increased by the CP treatment. CP (0.1 mM) also inhibited the in vitro metabolism of NE by 79%. These results provide experimental evidence in support of a hindered pulmonary clearance of circulating NE by CP.
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U2 - 10.3109/01902148109052304
DO - 10.3109/01902148109052304
M3 - Article
C2 - 7274178
AN - SCOPUS:0019797629
SN - 0190-2148
VL - 2
SP - 71
EP - 84
JO - Experimental Lung Research
JF - Experimental Lung Research
IS - 2
ER -