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Hypoxemia and elevated tachykinins in rat monocrotaline pneumotoxicity.

Abstract
This study was performed to test whether monocrotaline (MCT)-induced early airway dysfunction and gas exchange abnormalities result in arterial hypoxemia. Thirty young male Sprague-Dawley rats were divided into four groups: control, MCT1, MCT2, and MCT3. Each of the control animals was injected (subcutaneously) with saline; each of the MCT rats was injected with MCT (60 mg/kg, subcutaneously). The rats were tested 1 (MCT1), 2 (MCT2), or 3 (MCT3) weeks after MCT injection. Two days before each animal was tested, it was anesthetized with sodium pentobarbital, and its carotid artery was chronically cannulated. Blood was sampled from the arterial catheter of the conscious rat, and blood gases and pH were measured. Pulmonary arterial pressure (Ppa) was determined in the anesthetized, open chest animal. Heart weight was measured and a weight ratio obtained of right ventricle (RV) to left ventricle plus septum (LV+S). The amount of lung substance P and airway neutral endopeptidase (NEP) activity were also measured. MCT significantly decreased arterial oxygen tension (Pao2) and increased the RV/(LV+S) weight ratio 2 and 3 weeks after administration, whereas it did not significantly increase Ppa until 3 weeks after injection. MCT significantly increased lung substance P levels and decreased airway NEP activities 1-3 weeks after administration. These data suggest that tachykinins cause hypoxemia and RV hypertrophy; then hypoxia may augment the development of pulmonary hypertension.
AuthorsY L Lai, A A Thacker, J N Diana
JournalLung (Lung) Vol. 174 Issue 3 Pg. 195-203 ( 1996) ISSN: 0341-2040 [Print] United States
PMID8830195 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Substance P
  • Monocrotaline
  • Neprilysin
Topics
  • Animals
  • Hypertension, Pulmonary (blood, chemically induced, physiopathology)
  • Hypoxia (chemically induced)
  • Lung (metabolism)
  • Male
  • Monocrotaline
  • Neprilysin (metabolism)
  • Pulmonary Gas Exchange (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Substance P (metabolism)
  • Time Factors

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