title: 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 urethane-anesthetized, 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.
authors.affiliation: Department of Neurological Surgery, MSB H-586, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Vineet C
authors.initials: VC
authors.lastname: Chitravanshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hreday N
authors.initials: HN
authors.lastname: Sapru
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D017763:Autonomic Denervation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D017552:Solitary Nucleus / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology; D013127:Spinal Nerves / Q000502:physiology; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology; D014628:Vagotomy
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D017483:Receptors, Vasopressin; D016202:N-Methylaspartate