Na+/K(+)-adenosine triphosphatase activity of pulmonary arteries after intoxication with the pyrrolizidine alkaloid, monocrotaline.
Na+/K(+)-Adenosine triphosphatase-dependent activities of K(+)- return relaxation and 86Rb uptake were studied in pulmonary arteries taken from rats with pulmonary hypertension induced by monocrotaline. Rats were given monocrotaline in drinking water, 20 mg/l, for 4 or more days. Isolated arteries were placed in tissue baths and contracted with norepinephrine or 5-hydroxy-tryptamine under K(+)-free conditions. The arteries relaxed when K+ was "returned" to the bath. Compared to arteries from untreated rats, arteries taken from rats pretreated with monocrotaline developed less force in response to contracting agents and did not relax to the same extent. After 4 days treatment with monocrotaline, the rate of relaxation of the arteries in response to K(+)-return was slower than that of arteries taken from untreated rats. Endothelial trauma or in vitro treatment with ouabain produced a similar decrease in the rate of relaxation. Uptake of radiolabeled Rb by perfused arteries was not altered by 4 days of monocrotaline pretreatment. Isolated lungs taken from monocrotaline-pretreated rats (5 days of ingestion of 20 mg/l of monocrotaline drinking water) accumulated similar quantities of 86Rb+ during 40-sec perfusions. Shorter perfusion times, 10 and 20 sec, resulted in greater rates of uptake of 86Rb- by lungs taken from monocrotaline-treated rats. Monocrotaline produced changes in both the mechanical and biochemical properties of pulmonary arteries after only 4 to 5 days. These changes were associated with ouabain-sensitive processes. It appears, therefore, that one of the early targets in monocrotaline intoxication is the Na+/K+ pump of the pulmonary arteries.
Shubat
P J
PJ
Department of Pharmacology, College of Medicine, University of Arizona, Tucson.
Bowers
R J
RJ
Huxtable
R J
RJ
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D016686:Monocrotaline; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*; D014664:Vasodilation / Q000187:drug effects
D011763:Pyrrolizidine Alkaloids; D010042:Ouabain; D016686:Monocrotaline; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium