Excitatory Amino Acid Receptors in the Paraventricular Hypothalamic Nucleus Mediate Pressor Response Induced by Carotid Body Chemoreceptor Stimulation in Rats

Kubo, Takao; Yanagihara, Yasuho; Yamaguchi, Hiroaki; Fukumori, Ryuji

doi:10.3109/10641969709083208

Cited by 30 publications

(36 citation statements)

References 21 publications

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“…In contrast, intracerebroventricular administration of UII increased CBF. The cortical hemodynamic effect could be associated with the UII activation of different brain areas involved in cardiovascular regulation (Martin and Haywood, 1992;Kubo et al, 1997;Comer et al, 1998;Haywood et al, 2001). In fact, local injection of UII into the paraventricular nucleus, arcuate nucleus, and noradrenergic cells in the lower part of the medulla induces cardiovascular effects (Lu et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Huitrón‐Reséndiz

Kristensen²,

Sanchez‐Alavez³

et al. 2005

Journal of Neuroscience

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Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local administration of UII into the PPT nucleus increases REM sleep without inducing changes in the cortical blood flow. Intracerebroventricular injection of UII enhances both REM sleep and wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not local, administration of UII increases cortical blood flow. Moreover, whole-cell recordings from rat-brain slices show that UII selectively excites cholinergic PPT neurons via an inward current and membrane depolarization that were accompanied by membrane conductance decreases. This effect does not depend on action potential generation or fast synaptic transmission because it persisted in the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine receptors. Collectively, these results suggest that UII plays a role in the regulation of REM sleep independently of its cerebrovascular actions by directly activating cholinergic brainstem neurons.

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Section: Discussionmentioning

confidence: 99%

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Huitrón‐Reséndiz

Kristensen²,

Sanchez‐Alavez³

et al. 2005

Journal of Neuroscience

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“…To further support this notion, Kubo et al (1997) reported that the excitatory amino acid antagonist kynurenate injected into the PVN inhibited the chemoreceptor reflex-induced pressor response in anesthetized rats. Later, Olivan et al (2001) demonstrated bilateral electrolytic lesion of the PVN in conscious rats produced a significant reduction in the magnitude and duration of the pressor response induced by chemoreflex activation, suggesting that the PVN is involved in the regulation of cardiovascular responses to CB chemoreflex activation.…”

Section: Cb Chemoreflex At the Level Of The Paraventricular Nucleus Omentioning

confidence: 99%

“…Several studies have identified central neural structures involved in the sympathoexcitatory component of chemoreflexes; however, most have focused on the pons and the medulla (Guyenet 2000), which are the primary projection areas of chemosensitive afferents and the primary sites for respiratory and sympathetic integration. Apart from these areas of the brain, other studies suggest an involvement of the hypothalamus in modulating the respiratory and cardiovascular responses to hypoxia and hypercapnia (Horn & Waldrop 1994,Kubo et al 1997,Olivan et al 2001. In particular, hypoxia and hypercapnia stimulate neurons in various hypothalamic nuclei, including the PVN (Berquin et al 2000).…”

Section: Cb Chemoreflex At the Level Of The Paraventricular Nucleus Omentioning

confidence: 99%

Carotid body function in heart failure

Schultz

2007

Respiratory Physiology & Neurobiology

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In this review, we summarize the present state of knowledge of the functional characteristics of the carotid body (CB) chemoreflex with respect to control of sympathetic nerve activity (SNA) in chronic heart failure (CHF). Evidence from both CHF patients and animal models of CHF has clearly established that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in SNA. This adaptive change derives from altered function at the level of both the afferent and central nervous system (CNS) pathways of the reflex arc. At the level of the CB, an elevation in basal afferent discharge occurs under normoxic conditions in CHF rabbits, and the discharge responsiveness to hypoxia is enhanced. Outward voltage-gated K + currents (I K ) are suppressed in CB glomus cells from CHF rabbits, and their sensitivity to hypoxic inhibition is enhanced. These changes in I K derive partly from downregulation of nitric oxide synthase (NOS) / NO signaling and upregulation of angiotensin II (Ang II) / Ang II receptor (AT 1 R) signaling in glomus cells. At the level of the CNS, interactions of the enhanced input from CB chemoreceptors with altered input from baroreceptor and cardiac afferent pathways and from central Ang II further enhance sympathetic drive. In addition, impaired function of NO in the paraventricular nucleus of the hypothalamus participates in the increased SNA response to CB chemoreceptor activation. These results underscore the principle that multiple mechanisms involving Ang II and NO at the level of both the CB and CNS represent complementary and perhaps redundant adaptive mechanisms to enhance CB chemoreflex function in CHF.

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“…The following doses of the drugs were used: Kyn, 0.15 to 5 nmol/50 nL; AP5, 0.16 to 1.4 nmol/50 nL; CNQX, 0.22 to 1.8 nmol/50 nL; and gabazine, 0.3 to 10 nmol/50 nL. The microinjection doses for Kyn, 15,27 AP5, 15 CNQX, 29 and gabazine 30,31 were selected from previous studies and tested in the pilot experiments.…”

Section: Pvn Microinjectionsmentioning

confidence: 99%

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

2007

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Abstract-The paraventricular nucleus (PVN) of the hypothalamus is critical to the regulation of sympathetic output. The PVN hyperactivity is known to cause increased sympathetic nerve activity in spontaneously hypertensive rats (SHRs). The purpose of this study was to determine whether glutamatergic input to the PVN contributes to heightened sympathetic outflow in hypertension. Lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate were recorded from anesthetized SHRs and Wistar-Kyoto (WKY) rats. Bilateral microinjection of an N-methyl-Daspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid, or a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into the PVN dose-dependently decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Bilateral microinjection of kynurenic acid into the PVN also significantly decreased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in SHRs but not in WKY rats. Furthermore, microinjection of gabazine, a specific GABA A receptor antagonist, into the PVN increased lumbar sympathetic nerve activity, mean arterial blood pressure, and heart rate in both SHRs and WKY rats. Notably, this response was significantly attenuated in SHRs compared with that in WKY rats. In addition, kynurenic acid abolished the sympathoexcitatory and pressor responses to microinjection of gabazine into the PVN in both SHRs and WKY rats. Thus, this study provides new functional evidence that resting sympathetic vasomotor tone is maintained by tonic glutamatergic input in the PVN in SHRs. Removal of GABAergic inhibition results in augmented glutamatergic input in the PVN, which probably constitutes an important source of excitatory drive to the brain stem vasomotor neurons in hypertension. Key Words: excitatory amino acids Ⅲ hypothalamus Ⅲ sympathetic nervous system Ⅲ synaptic transmission Ⅲ autonomic nervous system Ⅲ NMDA receptors H ypertension is a significant risk factor for cardiovascular, renal, and cerebrovascular disorders. Increased sympathetic activity is often associated with hypertension and may contribute to the pathogenesis and maintenance of hypertension. 1,2 Previous studies suggested that altered central mechanisms are responsible for the elevated sympathetic outflow and arterial blood pressure in hypertension. In this regard, transection of the brain caudal to the hypothalamus reduces arterial blood pressure in spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. 3 The paraventricular nucleus (PVN) of the hypothalamus is an important region for the regulation of sympathetic output and arterial blood pressure. 4 -7 Lesions of the PVN in hypertensive rats, such as SHRs, Dahl salt-sensitive rats, and rats with renal hypertension, decrease blood pressure. 8 -11 Furthermore, inhibition of the PVN with muscimol reduces the blood pressure and sympathetic nerve activity in SHRs. 12 Thus, hyperactivity of PVN neurons may d...

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Excitatory Amino Acid Receptors in the Paraventricular Hypothalamic Nucleus Mediate Pressor Response Induced by Carotid Body Chemoreceptor Stimulation in Rats

Cited by 30 publications

References 21 publications

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Carotid body function in heart failure

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

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