Bioactivation of monocrotaline by P-450 3A in rat liver.

Monocrotaline (MCT) is bioactivated in liver cytochrome P-450s to MCT pyrrole (MCTP), which primarily injures the lung endothelium to result in the development of pulmonary hypertension (PH) in rats. However, whether there is a relation between the degree of PH and the activity of liver cytochrome P-450 to convert MCT to MCTP remains unclear. To examine the relation between these physiological and biochemical changes, we first measured the severity of MCT-induced (20 mg/kg) PH in male, female, castrated male, and phenobarbital (PB, liver P-450s inducer)-pretreated male rats.

[Interleukin-2 activity in monocrotaline-treated rat lungs].

To study the relationship between cytokines and the development of monocrotaline-induced pulmonary hypertension, monocrotaline was given and interleukin-2 was measured. The amount of interleukin-2 produced by pulmonary cells obtained by bronchoalveolar lavage was high only on the 14th day after monocrotaline injection (p < 0.01).

[Changes in smooth muscle cell proliferation in pulmonary arteries of rats given monocrotaline].

To study the relationship between proliferation of smooth muscle cells and structural changes in arteries of rats given monocrotaline, light microscopy with immunohistochemistry for bromodeoxyuridine (BrdU) was done after a single subcutaneous injection of monocrotaline. In increase in DNA synthesis in smooth muscle cells was seen from 3 days until 14 days after administration. Since this increase was seen before pulmonary hypertension and medial thickness developed some mechanisms that induce proliferation of pulmonary atrial smooth muscle may have been triggered soon after monocrotaline injection.

[Relationship between the converting ability of liver microsomes and monocrotaline-induced pulmonary hypertension in male, female and castrated male rats].

It is well known that the initial reaction of monocrotaline-induced pulmonary hypertension in rats (MPH) is injury to the endothelial cells of pulmonary vascular bed by monocrotaline-pyrrole (MP), which is converted from monocrotaline (M) by cytochrome P450 monooxygenase in hepatic microsomes. It is also known that the degree of MPH differs between sexes. The mechanisms of MPH remain, however, to be elucidated.

[Three-dimensional CT images of the lung--preliminary study using inflated lung specimens].

Three-dimensional CT images of six inflated lung specimens (4 lung cancer, 1 bronchiectasis, 1 hamartoma) were reconstructed from contiguous serial sections to study some probable problems in the clinical application of the technique. Optimal thickness and space of sections were evaluated, and contiguous 1.5-mm serial sections were found to provide a clear 3-D image with high fidelity.