Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia in rats.
The role of hypothalamic excitatory amino acid (EAA) receptors in mediating the cardiovascular response to stress was examined using conscious chronically instrumented rats. Microinjection of the EAA agonists N-methyl-D-aspartic acid (NMDA; 1-10 pmol), alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid (AMPA; 0.3-3.0 pmol), or kainic acid (0.1-1.0 pmol) into the dorsomedial hypothalamus (DMH) elicited dose-related increases in heart rate and modest elevations in arterial pressure. Local microinjection of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (AP5; 100 pmol) selectively blocked NMDA-induced cardiovascular changes, whereas the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 pmol) selectively blocked the responses to AMPA and kainic acid. In the stress trials, microinjection of the nonselective EAA antagonist kynurenic acid (1-10 nmol) into the DMH blocked air stress-induced tachycardia in a dose-related manner. Similar injection of kynurenic acid at sites lateral or posterior to the DMH or injection of xanthurenic acid (a structural analogue of kynurenic acid with no antagonistic properties at EAA receptors) into the DMH failed to influence air stress-induced cardiovascular changes. Injection of either AP5 or CNQX into the DMH at doses shown to be selective for their respective EAA receptor subtypes also attenuated air stress-induced tachycardia. Thus activity at EAA receptors in the DMH appears to be necessary for the generation of stress-induced changes in heart rate.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
R P
RP
Soltis
J A
JA
DiMicco
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007033:Hypothalamus, Middle / Q000378:metabolism*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*
D000596:Amino Acids; D009498:Neurotoxins; D011810:Quinoxalines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid