Abstract
1. We investigated the role of N-methyl-D-aspartic acid (NMDA) receptors in mediating hypoxic excitation of the reticulospinal vasomotor neurones of the rostroventrolateral reticular nucleus (RVL) of the medulla oblongata in paralysed ventilated rats. 2. Unilateral close arterial injection of sodium cyanide (100 nmol) into the carotid sinus region or ventilation with 100% N2 for 12 s rapidly, reversibly and reproducibly excited the RVL-spinal vasomotor neurones, followed about 1-2 s later by increases in sympathetic nerve activity and arterial pressure, effects abolished by denervation of the ipsilateral carotid sinus nerve. 3. Ionophoresis onto the RVL-spinal vasomotor neurones of kynurenate (a wide-spectrum antagonist of the excitatory amino acid receptors) or of 2-amino-5-monophosphovaleric acid (APV; a selective NMDA receptor antagonist), but not of xanthurenate (an inactive analogue of kynurenate), blocked the excitation elicited by intracarotid cyanide or 12 s of hypoxia. Kynurenate completely and APV partially blocked the excitatory responses to ionophoretically applied L-glutamate. APV, however, did not alter the excitatory responses of the vasomotor neurones to ionophoreses of kainate and quisqualate. 4. Bilateral microinjection of kynurenate (10 nmol, 50 nl per site) or APV (5 nmol, 50 nl per site) into the RVL blocked the increases in arterial pressure elicited by intracarotid cyanide or 12 s of 100% N2 ventilation. 5. Twenty seconds of intratracheal administration of 100% N2 resulted in complex and prolonged elevations of arterial pressure, the late component of which was affected neither by sinus denervation nor by microinjections of kynurenate or APV into the RVL. 6. We conclude that the sympathetic and cardiovascular responses to stimulation of arterial chemoreceptors result from excitation of RVL-spinal vasomotor neurones via activation of the NMDA subtypes of the excitatory amino acid receptors of the neurones. In contrast, the failure of these antagonists to influence the delayed excitation of the RVL-spinal vasomotor neurons by more prolonged exposure to N2 inhalation further supports the view that these neurones are directly stimulated by hypoxia.