Cardiorespiratory effects produced by blockade of excitatory amino acid receptors in cats.
The aim of our study was to determine the role of excitatory amino acids in controlling cardiorespiratory activity. For this purpose we administered an antagonist of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors (kynurenic acid), and an antagonist of the NMDA receptor complex (dizocilpine, more commonly known as MK-801) i.v. to chloralose-anesthetized cats while monitoring tracheal air flow, tidal volume, respiratory rate, inspiratory and expiratory durations, end tidal CO2, arterial blood pressure and heart rate. Administration of kynurenic acid in doses of 350 and 500 mg/kg produced respiratory depression as reflected by decreases in respiratory minute volume and increases in end tidal CO2. Inspiratory duration was increased with both doses and apnea (occurring during expiration) was observed with the high dose. Apnea was preceded by an apneustic pattern of breathing. Both doses resulted in an increase in blood pressure and, with the high dose, a later decrease in blood pressure was noted. Dizocilpine in doses ranging from 0.03 to 1 mg/kg produced dose-related decreases in respiratory minute volume, and increases in end tidal CO2. In addition, dizocilpine produced increases in inspiratory duration, an apneustic pattern of breathing and apnea (occurring during inspiration). Effects on blood pressure were similar to those observed with kynurenic acid. It is concluded that blockade of excitatory amino acid receptors results in pronounced effects on cardiorespiratory activity.
Abrahams
T P
TP
Department of Pharmacology, Georgetown University, School of Medicine, Washington, DC 20007.
Taveira DaSilva
A M
AM
Hamosh
P
P
McManigle
J E
JE
Gillis
R A
RA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002346:Carotid Sinus / Q000502:physiology; D002415:Cats; D003714:Denervation; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects; D014132:Trachea / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid