Mechanism of heart rate responses elicited by chemical stimulation of the hypothalamic paraventricular nucleus in the rat

Abstract

This study was designed to examine the mechanism of heart rate (HR) responses elicited by the stimulation of hypothalamic paraventricular nucleus (PVN). Experiments were done in urethaneanesthetized, barodenervated, adult, male Wistar rats. Chemical stimulation of the PVN by unilateral microinjections of N-methyl-D-aspartic acid (NMDA) elicited increases in HR which were attenuated by bilateral vagotomy. PVN-induced tachycardia was also attenuated by the blockade of the spinal ionotropic glutamate receptors (iGLURs) which was accomplished by intrathecal injections at T9-T10 or direct application at T1-T4 of iGLUR antagonists. The blockade of spinal iGLURs combined with bilateral vagotomy completely blocked PVN-induced tachycardia. Blockade of GABA receptors in the medial nucleus tractus solitarius (mNTS) also attenuated the PVN-induced tachycardia. Complete blockade of PVN-induced tachycardia was also observed after the blockade of iGLURs in both the spinal cord and mNTS. Combination of the blockade of mNTS GABA receptors and spinal iGLURs also abolished PVN-induced tachycardia. PVN-induced tachycardia was not altered by the blockade of spinal vasopressin or oxytocin receptors at T1-T4. These results suggested that in barodenervated rats: 1) tachycardia elicited by the chemical stimulation of the PVN was mediated via both inhibition of vagal and activation of sympathetic outflows to the heart, 2) the vagal inhibition contributing to the PVN-induced tachycardia was mediated by the iGLURs and GABARs in the mNTS, 3) sympathetic activation contributing to the PVN-induced tachycardia was mediated via spinal iGLURs, and 4) spinal vasopressin and oxytocin receptors were not involved in the mediation of PVN-induced tachycardia.

Cardiovascular Responses to Hypothalamic Arcuate Nucleus Stimulation in the Rat

“…After 20 minutes, a pledget of tissue paper soaked in combined solution of NBQX (2 mmol/L; 10 L) and D-AP7 (5 mmol/L; 10 L) was applied to the surface of the spinal cord at the T1 to T4 level. 8 Ten minutes later, the pressor responses (24.7Ϯ 3.9 mm Hg) to the ARCN stimulation were not altered significantly (PϾ0.05) after direct application of NBQX and D-AP7 at T1 to T4. On the other hand, the tachycardic responses (31.2Ϯ3.1 bpm) to the ARCN stimulation were significantly attenuated (58.3Ϯ1.6%; PϽ0.01), but not abolished, after the application of NBQX and D-AP7 at T1 to T4.…”

“…8 Combined solutions of the ionotropic glutamate receptor (iGLUR) antagonists (D(Ϫ)-2-amino-7-phosphonoheptanoic acid [D-AP7] and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione [NBQX] disodium salt) were injected intrathecally at T9 to T10 (volume: 20 L; duration: 10 seconds). Intrathecal injections (20 L) of artificial cerebrospinal fluid (aCSF) were used as controls.…”

“…8 The responses to ARCN stimulation were studied before and after the application of a tissue paper pledget soaked in combined iGLUR antagonist solution (20 L) to the spinal cord surface at T1 to T4. The spinal cord surface was irrigated with aCSF after the application of drugs and a fresh aCSF-soaked paper pledget was applied.…”

“…7,8 An expanded Methods section is available in the online Data Supplement at http://hyper.ahajournals.org.…”

Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation

“…However, the majority of responses are sympathoexcitatory, including studies performed in awake animals Haywood 1993, 1992) or when PVH neurons are disinhibited (Chen et al 2003;Kenney et al 2001;Li et al 2006;Haywood 1993, 1992;Martin et al 1991). Prior studies in anesthetized animals have reported that NMDA or non-NMDA receptor activation increases SNA and ABP (Kawabe et al 2008(Kawabe et al , 2009Kenney et al 2003; Ward et al 2011). Therefore, there was no a priori hypothesis regarding the relative contribution of NMDA vs. non-NMDA receptors in the sympathoexcitatory response to insulin.…”