Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia.
To elucidate further the role of the platelet in the development of monocrotaline pyrrole (MCTP)-induced lung injury and pulmonary hypertension, MCTP-treated rats were made thrombocytopenic by cotreatment with an anti-rat platelet serum (PAS). Lung injury was assessed from increases in lung weight, lavage fluid protein concentration, and lactate dehydrogenase activity and from accumulation in lung tissue of 125I-labeled albumin. These indexes of injury were not different in MCTP-treated rats with normal or reduced platelet numbers at day 4,8, or 14. In MCTP-treated rats not receiving the PAS, pulmonary arterial pressure was elevated by day 8. However, pulmonary arterial pressure was the same as controls at both day 8 and day 14 in MCTP-treated rats made moderately thrombocytopenic by cotreatment with PAS. More marked reduction of platelet number abolished the protective effect of thrombocytopenia against pulmonary hypertension. In a separate series of experiments, treatment with antibodies to platelet-derived growth factor (PDGF), a potential mediator in the response to MCTP-induced injury, did not protect rats from the cardiopulmonary effects of MCTP. These data indicate that moderate reduction of the number of circulating platelets prevents MCTP-induced pulmonary hypertension but not MCTP-induced lung injury, suggesting that the platelet is involved in the pulmonary hypertensive response to MCTP-induced lung injury by unknown mechanisms.
Ganey
P E
PE
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Sprugel
K H
KH
White
S M
SM
Wagner
J G
JG
Roth
R A
RA
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D001794:Blood Pressure; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology; D007116:Immunization, Passive; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000502:physiology; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D013921:Thrombocytopenia / Q000150:complications / Q000503:physiopathology*
D010982:Platelet-Derived Growth Factor; D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D007770:L-Lactate Dehydrogenase