Role of the dorsomedial hypothalamus in the cardiovascular response to stress.
1. Disinhibition of the dorsomedial hypothalamus (DMH) in rats by local microinjection of GABAA receptor antagonists evokes behavioural and physiological changes resembling those seen in acute experimental stress. 2. Conversely, similar microinjection of muscimol, a potent agonist at inhibitory GABAA receptors, virtually abolishes stress-induced increases in heart rate and arterial pressure. 3. Blockade of excitatory amino acid (EAA) receptors in the DMH also attenuates [correction of attentuates] stress-induced cardiovascular changes and microinjection of kainate, AMPA or NMDA at low doses elicits cardiovascular effects resembling those seen in stress. Paradoxically, injection of higher doses of NMDA or of glutamate into this region has no consistent effect. 4. The cardiovascular effects of bicuculline methiodide, a GABAA receptor antagonist, as well as those of NMDA and/or kainate were assessed after identical injection into either the DMH, the paraventricular nucleus (PVN) or the area between the two nuclei in both anaesthetized and conscious rats. For each agent, a similar pattern was seen, with the largest increases in heart rate and arterial pressure occurring after injection into the DMH and the smallest changes resulting from injection into the PVN. 5. In a parallel study, bilateral microinjection of muscimol into the DMH dramatically reduced air stress-induced cardiovascular changes; similar injection into the area of the PVN had no effect, while injection into the area between the nuclei produced an intermediate effect. 6. Our findings suggest that activation of neurons in the region of the DMH mediates stress-induced cardiovascular changes and that the activity of these neurons may be determined by the balance of tone at inhibitory GABAA receptors and EAA receptors.
DiMicco
J A
JA
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202, USA.
Stotz-Potter
E H
EH
Monroe
A J
AJ
Morin
S M
SM
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004302:Dorsomedial Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*
D018690:Excitatory Amino Acid Agonists