Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats.
To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets.
White
S M
SM
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Wagner
J G
JG
Roth
R A
RA
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004126:Dimethylformamide / Q000494:pharmacology; D006454:Hemoglobins / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives*; D010976:Platelet Count; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013156:Splenectomy
D006454:Hemoglobins; D007205:Indium Radioisotopes; D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D004126:Dimethylformamide