Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats

Verberne, Anthony J.M.; Widdop, Robert E; Maccarrone, C.; Jarrott, Bevyn; Beart, Philip M; Louis, William J.

doi:10.1016/0304-3940(90)90582-t

Cited by 26 publications

(17 citation statements)

References 20 publications

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“…KYN decreased arterial pressure in water replete rats ϳ20 mmHg with the maximum fall occurring at ϳ15 min. This is a smaller and faster response than that reported by Verberne et al (40) using the same dose of KYN in conscious rats. Similarly, the HR response we observed in the water-replete rats was smaller and faster than that reported by Verberne et al (40).…”

Section: Effect Of It Kyn On Arterial Pressure and Hr Before And Ducontrasting

confidence: 68%

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Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Veitenheimer

Osborn

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Increased plasma osmolality elevates mean arterial pressure (MAP) through activation of the sympathetic nervous system, but the neurotransmitters released in the spinal cord to regulate MAP during osmotic stress remain unresolved. Glutamatergic neurons of the rostral ventrolateral medulla project to sympathetic preganglionic neurons in the spinal cord and are likely activated during conditions of osmotic stress; however, this has not been examined in conscious rats. This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a greater fall in MAP in response to i.t. 2-amino-5-phosphonovalerate. Finally, i.t. kynurenic acid also decreased MAP more in an osmotically driven model of neurogenic hypertension, the DOCA-salt rat, compared with normotensive controls. Our results suggest that spinally released glutamate mediates increased MAP during 48-h WD and DOCA-salt hypertension.

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Section: Effect Of It Kyn On Arterial Pressure and Hr Before And Ducontrasting

confidence: 68%

“…The dose of i.t. KYN (50 mM) was based on a previously published study (40). KYN was dissolved in NaOH and titrated to a final pH of 7.4.…”

Section: Experimental Protocolsmentioning

confidence: 99%

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Veitenheimer

Osborn

2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…This projection is thought to mainly originate in the rostral ventrolateral medulla (RVLM, Morrison et al 1991;Mills et al 1990;Verberne et al 1990;Bazil & Gordon, 1991;Sundaram & Sapru, 1991;Kapoor et al 1992;Deuchars et al 1995). Since these RVLM neurones can be activated by stimulating neurones in the PVN (Yang & Coote, 1998), they may have participated in the PVN-induced excitatory effects on RSNA, which were blocked by intrathecal application of the broad spectrum ionotropic receptor antagonist kynurenic acid in the present experiments.…”

Section: Pvn-spinal Receptorsmentioning

confidence: 55%

Neuropeptides, Amines and Amino Acids as Mediators of the Sympathetic Effects of Paraventricular Nucleus Activation in the Rat

Yang¹,

Wheatley

Coote³

2002

Experimental Physiology

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The aim of the present study was to determine the influence on renal sympathetic nerve activity of the different chemically coded neuronal phenotypes that project from the paraventricular nucleus (PVN) to the spinal cord. Experiments were carried out on male Wistar rats anaesthetised with chloralose and urethane. Changes in renal sympathetic nerve activity were measured following activation of neurones in the PVN with D,L-homocysteic acid (100 nl, 200 mM), before and following intrathecal application of glutamate, vasopressin, oxytocin, dopamine and their receptor antagonists. Excitatory and inhibitory effects on renal sympathetic nerve activity were elicited by PVN stimulation. PVN excitatory effects were mimicked by intrathecal administration of glutamate and vasopressin and selectively antagonised by intrathecal administration of kynurenic acid and a V 1a receptor antagonist, respectively. A low dose of dopamine increased renal sympathetic activity and this was selectively antagonised by haloperidol; however, the latter was without effect on PVN excitatory responses. A high dose of dopamine decreased renal sympathetic nerve activity and this was selectively blocked by a D1 dopamine receptor antagonist (SCH 23390), which also antagonised a minority of inhibitory responses obtained from the caudal extension of the PVN. Oxytocin also had two actions: in 5 rats it inhibited and in 10 rats it increased renal sympathetic nerve activity, both actions being blocked selectively by oxytocin receptor antagonists. Neither of the PVN effects on renal sympathetic nerve activity appeared to be dependent on oxytocin pathways. Tests with intrathecal administration of bicuculline showed that PVN inhibition of renal sympathetic nerve activity was not dependent on spinal GABA A receptor activation. The results show that PVN-induced excitation of sympathetic activity to the kidney is mainly mediated by glutamate or vasopressin neurones whereas dopamine via D1 receptors may mediate some of the PVN inhibitory effects. Experimental Physiology (2002) METHODSThe experiments were approved by the local ethical committee of the University of Birmingham and were performed under a Home Office Licence in accordance with the UK Animals (Scientific Procedures) Act 1986. Animal preparationThe experiments were performed on 52 male rats (Wistar) weighing 292 ± 4.0 g, anaesthetised with a mixture of urethane and a-chloralose (650 mg kg _1 and 50 mg kg _1 , respectively) given I.V. after initial induction with enflurane. An adequate depth of anaesthesia was ensured by observing arterial blood pressure, heart rate and the absence of corneal and paw-pinch reflexes, and was maintained by regular hourly administration of additional anaesthetic (I.V.), or sooner if needed. The femoral artery was cannulated with a polyethylene catheter (PE-50 tubing) which was connected to a pressure transducer for continuous recording of arterial blood pressure. A femoral vein was also cannulated for administration of drugs.

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“…Glutamate antagonists profoundly affect autonomic responses mediated by SPN and PPN. Injection of kynurenate, a broad-spectrum glutamate receptor antagonist, into the subarachnoid space of the thoracic cord dramatically reduces arterial pressure and heart rate (Verberne et al, 1990), and local application of kynurenate decreases the spontaneous activity of individually recorded SPN (Morrison, 2003). In addition, antagonism of glutamatergic receptors in the spinal cord reduces the sympathoexcitatory and pressor responses produced by stimulation of the rostral ventrolateral medulla (RVLM; Mills et al, 1988;Sun and Reis, 1994;Morrison, 2003).…”

mentioning

confidence: 99%

VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord

Llewellyn‐Smith

Martin

Fenwick

et al. 2007

J of Comparative Neurology

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Fast excitatory neurotransmission to sympathetic and parasympathetic preganglionic neurons (SPN and PPN) is glutamatergic. To characterize this innervation in spinal autonomic regions, we localized immunoreactivity for vesicular glutamate transporters (VGLUTs) 1 and 2 in intact cords and after upper thoracic complete transections. Preganglionic neurons were retrogradely labeled by intraperitoneal Fluoro-Gold or with cholera toxin B (CTB) from superior cervical, celiac, or major pelvic ganglia or adrenal medulla. Glutamatergic somata were localized with in situ hybridization for VGLUT mRNA. In intact cords, all autonomic areas contained abundant VGLUT2-immunoreactive axons and synapses. CTB-immunoreactive SPN and PPN received many close appositions from VGLUT2-immunoreactive axons. VGLUT2-immunoreactive synapses occurred on Fluoro-Gold-labeled SPN. Somata with VGLUT2 mRNA occurred throughout the spinal gray matter. VGLUT2 immunoreactivity was not noticeably affected caudal to a transection. In contrast, in intact cords, VGLUT1-immunoreactive axons were sparse in the intermediolateral cell column (IML) and lumbosacral parasympathetic nucleus but moderately dense above the central canal. VGLUT1-immunoreactive close appositions were rare on SPN in the IML and the central autonomic area and on PPN. Transection reduced the density of VGLUT1-immunoreactive axons in sympathetic subnuclei but increased their density in the parasympathetic nucleus. Neuronal cell bodies with VGLUT1 mRNA occurred only in Clarke's column. These data indicate that SPN and PPN are densely innervated by VGLUT2-immunoreactive axons, some of which arise from spinal neurons. In contrast, the VGLUT1-immunoreactive innervation of spinal preganglionic neurons is sparse, and some may arise from supraspinal sources. Increased VGLUT1 immunoreactivity after transection may correlate with increased glutamatergic transmission to PPN.

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Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats

Cited by 26 publications

References 20 publications

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats

Neuropeptides, Amines and Amino Acids as Mediators of the Sympathetic Effects of Paraventricular Nucleus Activation in the Rat

VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord

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