Article date: 1992/3/1
PubMed ID: 1375523
Journal name: Brain research bulletin (ISSN: 0361-9230)
Injection of ibotenic acid (IA), a glutamate agonist, into the ventral medullary raphe (VMR; especially the nucleus raphe magnus) of the rat produced respiratory failure and death following a predictable course of events. The response to the IA injection was characterized initially by increased respiratory frequency and was followed by pulmonary arterial hypertension, systemic arterial hypoxemia, acidosis, and hypothermia. Within 90 min apnea occurred as a terminal event in all animals. Gravimetric, bronchoalveolar lavage protein, and histological analyses revealed no evidence of pulmonary edema. Intracerebral (VMR) pretreatment with PPP, a sigma receptor agonist, or scopolamine, a muscarinic cholinergic antagonist, prevented pulmonary failure and death even though postmortem histological analysis showed VMR cell loss and gliosis consequent to the cytotoxic IA injection. Based on the results of the study, it is suggested that the VMR has a role in regulation of pulmonary blood flow. Preliminary pharmacological studies suggested that a disruption of glutamatergic and cholinergic mechanisms mediates the lethal pulmonary phenomenon.
Author List: Carruth M K, Fowler A A, Fairman R P, Mayer D J, Leichnetz G R
Publication Types: Journal Article
Substances mentioned in the article: Glutamates; Ibotenic Acid; Glutamic Acid;
Mesh terms: Animals; Blood Gas Analysis; Blood Pressure/drug effects; Body Temperature/drug effects; Bronchoalveolar Lavage Fluid/metabolism; Drug Interactions; Glutamates/physiology; Glutamic Acid; Ibotenic Acid/administration & dosage; Injections; Lung/anatomy & histology; Male; Medulla Oblongata/anatomy & histology; Models, Biological; Pulmonary Edema/physiopathology; Pulmonary Wedge Pressure/drug effects; Rats; Rats, Inbred Strains; Respiratory Insufficiency/chemically induced; Staining and Labeling;