Cardiovascular function of a glutamatergic projection from the hypothalamic paraventricular nucleus to the nucleus tractus solitarius in the rat

Abstract

Experiments were done in urethane-anesthetized, barodenervated, male Wistar rats. Chemical stimulation of the hypothalamic paraventricular nucleus (PVN) by unilateral microinjections of Nmethyl-D-aspartic acid (NMDA) elicited increases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA). The increases in the MAP and GSNA induced by chemical stimulation of the PVN were significantly exaggerated by bilateral microinjections of D-AP7 and NBQX (ionotropic glutamate receptor antagonists) into the medial subnucleus of the nucleus tractus solitarius (mNTS). These results were confirmed by single unit recordings; i.e., excitation of mNTS barosensitive neurons caused by chemical stimulation of the ipsilateral PVN was blocked by application of D-AP7 and NBQX to these neurons. Bilateral microinjections of D-AP7 and NBQX into the mNTS elicited pressor responses which were significantly attenuated by inhibition of PVN neurons by bilateral microinjections of muscimol. Unilateral microinjections of fluorogold into the mNTS resulted in bilateral retrograde labeling of the PVN neurons. Unilateral microinjections of biotinylated dextran amine into the PVN resulted in anterograde labeling of axons and terminals in the mNTS bilaterally and the labeled terminals exhibited vesicular glutamate transporter-2 immunoreactivity. These results indicated that; 1) a tonically active glutamatergic bilateral projection from the PVN to the mNTS exists, 2) bilateral blockade of ionotropic glutamate receptors in the mNTS exaggerates the increases in MAP and GSNA to the chemical stimulation of the PVN, and 3) this projection may serve as a restraint mechanism for excitatory cardiovascular effects of PVN stimulation.

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

“…Emerging evidence, however, has indicated that the hippocampus and hypothalamic paraventricular nucleus, which project into the cardiac regulatory centers, also play a significant role in regulating cardiovascular function. 32 This finding is supported by earlier studies showing that injection of kainic acid or NMDA into the paraventricular nucleus resulted in lesions of the parvocellular elements and evoked an excitotoxin-induced myocardial necrosis resembling the acute myocardial necrosis reported with systemic ␤-agonist administration. [33][34][35] These studies support the hypothesis that the reported cardiotoxicity is a consequence of a catecholamine surge mediated by excitotoxin stimulation of glutamate receptors in the CNS.…”

GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

“…The onset, peak, and duration of tachycardic responses (16 Ϯ 3 s, 3 Ϯ 1 min, and 13 Ϯ 2 min, respectively) were not statistically different from those of depressor responses. These time intervals are similar to those previously reported by us and others after microinjections of NMDA into the ARCN or PVN (24,26,30). In the ARCN, all microinjections were unilateral, and the volume of microinjections was 30 nl.…”

Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching

“…Prior to testing, rats remained in their home cages for 5 min after completion of the injection procedure to allow for the drug to take effect (Hikosaka and Wurtz 1985;Krupa et al 1999;Palencia and Ragozzino 2004;Baker and Ragozzino 2014). Past studies have shown that microinjections of GABA agonists or glutamate antagonists into specific brain structures can act within a couple of minutes to decrease neural activity and last well over 40 min (Kawabe et al 2008;McMullan and Pilowsky 2012). As in past studies (McCool et al 2008;Brown et al 2010), the day prior to the first test procedure, an injection cannula was lowered into each guide cannula and left in place for 2 min.…”