Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia in rats

Abstract

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.

Angiotensin II in dorsomedial hypothalamus modulates cardiovascular arousal caused by stress but not feeding in rabbits

“…The present study indicates that the DMH plays a crucial role in regulating autonomic cardiovascular arousal caused by emotional stress in rabbits, in line with previous findings in rats (33,35,38). The present results also provide, to our knowledge, the first evidence that the DMH is critical in mediating cardiovascular arousal associated with appetitive feeding behavior.…”

“…It has been shown that cardiovascular arousal evoked by blockade of GABAergic inhibition in the DMH or by emotional stress depends on activation of local EAA receptors in rats (35,36). Similarly, in our study, microinjection of an EAA antagonist, kynurenic acid, into the DMH effectively decreased the pressor response to air-jet stress.…”

“…In 10 other animals, the same doses of muscimol (n ϭ 8), candesartan (n ϭ 4), kynurenic acid (n ϭ 2), and vehicle (n ϭ 3) were injected outside the DMH to assess the anatomic specificity of the stress and eating responses. The selected doses of the drugs were based on our laboratory's earlier experiments (22,24,25) and on previous studies from other laboratories (13,35). Each rabbit was subjected to one to two different treatments per experimental day.…”

Panic-Prone State Induced in Rats with GABA Dysfunction in the Dorsomedial Hypothalamus Is Mediated by NMDA Receptors

“…This is in contrast to the physiological responses elicited by acute GABA blockade in the DMH, where both NMDA and AMPA receptor antagonists are partially effective in blocking the physiological responses (Soltis and DiMicco, 1991), and injection of NMDA and AMPA receptor agonists into the DMH elicits panic-like physiological and behavioral responses (Soltis and DiMicco, 1992). It appears that chronic reduction of GABA inhibition results in long-term adaptation of the glutamate neurotransmission in this region, resulting in a dominance of the NMDA-mediated excitatory neurotransmission.…”

Microinjection of muscimol into the periaqueductal gray suppresses cardiovascular and neuroendocrine response to air jet stress in conscious rats

“…Although these peripheral changes have been well characterized, the central pathways and mechanisms involved in their generation have only been recently and incompletely elucidated. One of the paradigms that has been employed in studies of these central mechanisms is air jet stress, which has been shown to elicit all of the above changes in conscious rats (2,29,44,46,47,54). Depending upon the exact model employed, air jet stress may involve elements of psychological, physical, and even cold stress.…”