title: Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats.
abstract: Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.
authors.affiliation: The Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Veitenheimer
authors.forename: John W
authors.initials: JW
authors.lastname: Osborn
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D062186:Arterial Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D003243:Consciousness; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D018698:Glutamic Acid / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007278:Injections, Spinal; D007736:Kynurenic Acid / Q000008:administration & dosage*; D008297:Male; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013312:Stress, Physiological; D013686:Telemetry; D013997:Time Factors; D014868:Water Deprivation
chemical_list: D000959:Antihypertensive Agents; D018691:Excitatory Amino Acid Antagonists; D058468:Receptors, Ionotropic Glutamate; D018698:Glutamic Acid; D003900:Desoxycorticosterone; D007736:Kynurenic Acid