Mz. Goren et al., Participation of NMDA and kainate receptors of paraventricular nucleus in cardiovascular responses to glutamate receptor agonist, EUR J PHARM, 388(1), 2000, pp. 77-84
The nuclei of the hypothalamus have been shown to be involved in central ca
rdiovascular homeostasis. Recent studies suggest that glutamate-containing
neurons have an important role in the regulation of central cardiovascular
function. We report first on the effects of intracerebrally injected NMDA a
nd non-NMDA receptor ligands on blood pressure and heart rate in conscious
Sprague-Dawley rats. In the second part, we describe the effect of blockade
of NMDA or kainate receptors in the paraventricular nucleus on glutamate r
eceptor agonist-induced blood pressure responses. Intracerebroventricular i
njections of L-glutamic acid, NMDA and kainic acid produced increases in me
an arterial pressure, Kainic acid produced significant decreases in heart r
ate. Microinjection of DL-2-amino-5-phosphonopentanoic acid (APV; 25 and 50
nmol), a competitive NMDA receptor antagonist, into the paraventricular nu
cleus blunted the increases in the mean arterial pressure evoked by intrace
rebroventricular injections of NMDA (1 nmol), whereas microinjection of din
itroquinoxaline (DNQX; 20, 40 and 80 pmol), which acts as an antagonist at
kainate receptors, failed to antagonize the cardiovascular effects of intra
cerebroventricular kainic acid (10 pmol). Microinjections of NMDA (100 pmol
) into the paraventricular nucleus produced presser responses, but kainic a
cid (5 and 10 pmol) failed to affect either mean arterial pressure or heart
rate. These results suggest participation of the glutamergic system in car
diovascular regulation via NMDA receptors located within the paraventricula
r nucleus of the hypothalamus in rats. (C) 2000 Elsevier Science B.V. All r
ights reserved.