Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1993-8-11
pubmed:abstractText
Dietary restriction (DR), i.e. reduction of total caloric intake, has been shown to result in protection against monocrotaline (MCT)-induced pulmonary hypertension (PH). Restriction of the diet to 8 g/rat/day instead of the usual intake (18 g/rat/day), inhibits the progression of cardiopulmonary changes and prolongs survival after a single dose of MCT. We have shown previously that the development of MCT-induced pulmonary hypertension is associated with inhibition of polyamine biosynthesis in the lungs of MCT-treated rats. In the present study, we tested the hypothesis that DR provides protection against the development of chronic PH in the rat by limiting increases in polyamine and DNA synthesis. We randomly divided animals into four groups each (MCT, MCT + DR, control, and control + DR). We injected rats with a single dose of MCT (60 mg/kg, s.c.) and a corresponding number of control rats with vehicle. Animals in all groups were given free access to food and water prior to administration of MCT. Immediately following injection of MCT both the MCT and control groups were given free access to food and water, while the other groups (MCT + DR and control + DR) we given the restricted diet (8 g/rat/day). Daily measurements were made of body weight and of water and food intake. Animals were killed in each group at 1, 4, 7, 14, and 21 days post MCT to determine right ventricular hypertrophy (RVH), lung wet weight, ornithine decarboxylase (ODC) activity, and polyamine and DNA contents. We measured DNA synthesis 7 days after MCT by determining [3H]thymidine incorporation into the whole lung DNA. We found that 7 days after MCT treatment DNA synthesis increased compared to control. However, DR (MCT + DR) treatmen prevented the increase in DNA synthesis following MCT. Right ventricular hypertrophy, lung wet weight, ODC activity and lung polyamine levels were increased following MCT. Treatment with DR (MCT + DR) prevented increases in RVH, lung wet weight, ODC activity and lung polyamine levels. We conclude that DR to 8 g/day/rat protects against MCT-induced PH and is associated with an inhibition of increased lung polyamine and DNA synthesis that occur in the lung during the development of MCT-induced PH. These results are consistent with a recent report which suggests that increased lung polyamine biosynthesis is required for the development of MCT-induced PH. The data are also consistent with the hypothesis that inhibition of polyamine biosynthesis influences the development of MCT-induced PH in part by regulating DNA synthesis in key lung cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2475-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Dietary restriction, polyamines and monocrotaline-induced pulmonary hypertension.
pubmed:affiliation
Department of Medicine, University of California, Los Angeles.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't