Intrathecal administration of non-NMDA receptor agonists increases arterial pressure and heart rate in the rat

Abstract

We have found that spinal NMDA receptors are involved in control of sympathetic output in pathways to the heart and vessels. The present study was done to determine whether spinal non-NMDA excitatory amino acid receptors participate in cardiovascular regulation. Experiments were done on urethane-anesthetized Sprague-Dawley rats, giving the non-NMDA receptor agonists, quisqualate and kainate, and the antagonist, kynurenate, intrathecally at the spinal T 9 level. Both quisqualate (30 nmol; n = 7; to activate AMPA receptors) and kainate (2 nmol; n = 6; to activate K receptors) increased arterial pressure and heart rate. The responses were characterized by a rapid onset, achieving, in most cases, > 80% of the maximum response within 1–4 min, and a persistence throughout the remaining 20–24 min of the experiment. I.v. injection of hexamethonium (10 mg/kg) prevented the effects of intrathecal administration of quisqualate ( n = 5) but not of kainate ( n = 7). To determine whether the hexamethonium-resistant effects of kainate were due to a peripheral action, kainate was given i.v. ( n = 6); it was found to be without effect on arterial pressure or heart rate. The increases in arterial pressure and heart rate produced by intrathecal administration of quisqualate (30 nmol; n = 6), kainate (2 nmol; n = 6), glutamate (1 μmol; n = 6) and NMDA (2 nmol; n = 6) but not carbachol (27.4 nmol; n = 6) were prevented by similar preadministration of kynurenate (125 nmol). Intrathecal administration of kynurenate (125 nmol; n = 6; 500 nmol; n = 7) decreased arterial pressure and/or heart rate. The greatest decreases in the group given the higher dose occurred at about 10 min (systolic pressures, 26.7 ± 1.5 mmHg; diastolic pressure, 13.6 ± 1.8 mmHg) and 4 min (heart rate, 13.3 ± 5.0 bpm). These responses persisted for 7–25 min. The results indicate: (1) spinal non-NMDA receptors are involved in activation of sympathetic output regulating cardiovascular function; (2) pathways activated by quisqualate and by kainate at the spinal level are mediated in sympathetic ganglia via nicotinic and non-nicotinic mechanisms, respectively; (3) there appears to be a tonic activation of non-NMDA receptors in pathways to the heart.