Strain differences in the response of Fischer 344 and Sprague-Dawley rats to monocrotaline induced pulmonary vascular disease

L. C. Pan, Dennis W Wilson, H. J. Segall

Research output: Contribution to journalArticle

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Abstract

The pyrrolizidine alkaloid (PA) monocrotaline (MCT) is thought to be activated in the liver to monocrotaline pyrrole (MCTP) which is then transported to the lungs where it causes a pulmonary vascular syndrome characterized by elevated pulmonary artery pressure and right ventricular hypertrophy. We have found that, as opposed to Sprague-Dawley (SD) rats, Fischer 344 (F344) strain rats are resistant to the ventricular hypertrophy and pressure changes induced by MCT. To determine whether this strain difference might be related to differences in hepatic activation of MCT to MCTP, we compared the response of SD and F344 rats to treatment with MCT or MCTP. We determined right ventricular pressure and ventricular weight ratios with each treatment for each strain. We also compared subjective lesion scores of histopathologic changes characteristic of MCT pneumotoxicity. Sprague-Dawley rats treated with either MCT or MCTP had elevated right ventricular pressures Control 13 ± 1 mmH2O, MCTP 29 ± 3 mmH2O, MCT 24 ± 2 mmH2O) and increased right ventricular weight ratio (RV/LV + S) of 0.30 ± 0.01 (Control), 0.44 ± 0.05 (MCTP), 0.44 ± 0.02 (MCT). Histopathologic evaluation demonstrated that significant alveolar septal fibrosis, edema and type II cell hypertrophy was induced by both PAs in both rat strains but that F344 rats had significantly less vascular medial hypertrophy and adventitial inflammation than SD rats. MCTP treated SD rats had similar vascular and parenchymal alterations as those treated with MCT but with a lessor inflammatory component. We conclude that the strain differences in cardiac and pulmonary vascular responses to MCT also occur with MCTP treatment. This, combined with the similarity in alveolar parenchymal response to both PAs in both strains, suggests that these differences are related to the pulmonary vascular response rather than differences in hepatic metabolism.

Original languageEnglish (US)
Pages (from-to)21-35
Number of pages15
JournalToxicology
Volume79
Issue number1
DOIs
StatePublished - Mar 30 1993

Fingerprint

Monocrotaline
Vascular Diseases
Lung Diseases
Sprague Dawley Rats
Rats
Blood Vessels
Ventricular Pressure
Hypertrophy
Lung
Inbred F344 Rats
Liver
Pyrrolizidine Alkaloids
Right Ventricular Hypertrophy
Weights and Measures
Adventitia
Pressure control
monocrotaline pyrrole
Metabolism
Pulmonary Artery
Edema

Keywords

  • Monocrotaline
  • Pathology
  • Pulmonary Hypertension
  • Rats
  • Strain Differences

ASJC Scopus subject areas

  • Toxicology

Cite this

Strain differences in the response of Fischer 344 and Sprague-Dawley rats to monocrotaline induced pulmonary vascular disease. / Pan, L. C.; Wilson, Dennis W; Segall, H. J.

In: Toxicology, Vol. 79, No. 1, 30.03.1993, p. 21-35.

Research output: Contribution to journalArticle

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