Low-dose PGI2 prevents monocrotaline-induced thromboxane production and lung injury.
In animals, monocrotaline induces an acute lung injury secondary to capillary endothelial damage. To date, no reports have appeared dealing with the role of prostaglandins in monocrotaline-induced injury. Our studies, in dogs, revealed that monocrotaline (30 mg/kg iv) caused an acute and persistent thrombocytopenia, lung platelet deposition, pulmonary hypertension, and increased extravascular lung water (EVLW). The pulmonary hypertensive response was biphasic. Thromboxane B2 levels were similarly biphasic, peaking at 5 min and 2 h. The levels of 6-keto-PGF1 alpha peaked at 30 min and returned to base line at 3 h. Pulmonary vascular resistance paralleled thromboxane levels. Infusion of prostacyclin (PGI2) at 50 ng X kg-1 X min-1 effectively prevented the thrombocytopenia, lung platelet deposition, pulmonary hypertension, and increased EVLW; and it decreased excess thromboxane production by 79%. These results suggest that platelet activation and lung sequestration play a role in acute lung injury due to monocrotaline, and that the resultant thromboxane production may contribute to the pulmonary hypertension. PGI2 ameliorates monocrotaline-induced injury, perhaps by preventing platelet activation.
Czer
G T
GT
Marsh
J
J
Konopka
R
R
Moser
K M
KM
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001772:Blood Cell Count; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000517:prevention & control; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D016686:Monocrotaline; D011763:Pyrrolizidine Alkaloids / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D013929:Thromboxane B2 / Q000096:biosynthesis*
D011763:Pyrrolizidine Alkaloids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016686:Monocrotaline; D011464:Epoprostenol