Involvement of Nitric Oxide in Cardiorespiratory Regulation in the Nucleus Tractus Solitarii

Vitagliano, S.; Berrino, Liberato; D’Amico, Michele; Maione, Sabatino; Novellis, Vito de

doi:10.1016/0028-3908(96)84633-8

Cited by 27 publications

(31 citation statements)

References 27 publications

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“…Both inhibitory (32,33) and stimulatory (34)(35)(36) effects of NOS activation have been described that reflect the differing actions of NO and S-nitrosothiols, respectively. nNOS activity is dynamically regulated (inhibited) by S-nitrosylation at cysteine 331 (20).…”

Section: Nos Expression Function and S-nitrosylation Statusmentioning

confidence: 99%

Hypoxia-Induced Changes in Protein S-Nitrosylation in Female Mouse Brainstem

Palmer

deRonde

Brown-Steinke

et al. 2015

Am J Respir Cell Mol Biol

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Exposure to hypoxia elicits an increase in minute ventilation that diminishes during continued exposure (roll-off). Brainstem Nmethyl-D-aspartate receptors (NMDARs) and neuronal nitric oxide synthase (nNOS) contribute to the initial hypoxia-induced increases in minute ventilation. Roll-off is regulated by platelet-derived growth factor receptor-b (PDGFR-b) and S-nitrosoglutathione (GSNO) reductase (GSNOR). S-nitrosylation inhibits activities of NMDAR and nNOS, but enhances GSNOR activity. The importance of S-nitrosylation in the hypoxic ventilatory response is unknown. This study confirms that ventilatory roll-off is virtually absent in female GSNOR 1/2 and GSNO 2/2 mice, and evaluated the location of GSNOR in female mouse brainstem, and temporal changes in GSNOR activity, protein expression, and S-nitrosylation status of GSNOR, NMDAR (1, 2A, 2B), nNOS, and PDGFR-b during hypoxic challenge. GSNOR-positive neurons were present throughout the brainstem, including the nucleus tractus solitarius. Protein abundances for GSNOR, nNOS, all NMDAR subunits and PDGFR-b were not altered by hypoxia. GSNOR activity and S-nitrosylation status temporally increased with hypoxia. In addition, nNOS Snitrosylation increased with 3 and 15 minutes of hypoxia. Changes in NMDAR S-nitrosylation were detected in NMDAR 2B at 15 minutes of hypoxia. No hypoxia-induced changes in PDGFR-b Snitrosylation were detected. However, PDGFR-b phosphorylation increased in the brainstems of wild-type mice during hypoxic exposure (consistent with roll-off), whereas it did not rise in GSNOR 1/2 mice (consistent with lack of roll-off). These data suggest that: (1) S-nitrosylation events regulate hypoxic ventilatory response; (2) increases in S-nitrosylation of NMDAR 2B, nNOS, and GSNOR may contribute to ventilatory roll-off; and (3) GSNOR regulates PDGFR-b phosphorylation.Keywords: hypoxic ventilatory response; neuronal nitric oxide synthase; N-methyl-D-aspartate receptor; platelet-derived growth factor receptor-b; S-nitrosoglutathione reductase Clinical RelevanceThis article reports that the change in S-nitrosylation status of key brainstem proteins may underlie the roll-off phase of the hypoxic ventilatory response. This has potential clinical applications for understanding how mechanisms that affect S-nitrosothiol bioavailability (i.e., S-nitrosoglutathione reductase) play a role in central breathing disorders.

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Section: Nos Expression Function and S-nitrosylation Statusmentioning

confidence: 99%

Hypoxia-Induced Changes in Protein S-Nitrosylation in Female Mouse Brainstem

Palmer

deRonde

Brown-Steinke

et al. 2015

Am J Respir Cell Mol Biol

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“…40,41 Data are also inconsistent when either NO donors or L-arginine are microinjected into the NTS (no change 40,42 or decreased [43][44][45][46][47][48] ). Previous studies describing the effects of NOS inhibitors in the NTS on baroreceptor reflex gain are also inconsistent (no change, 40,49 increased, 39 or decreased 38,50,51 ).…”

Section: Diversity Of Effects Of Nitrergic Mechanisms In the Nts For mentioning

confidence: 99%

Endothelial NO Synthase Activity in Nucleus Tractus Solitarii Contributes to Hypertension in Spontaneously Hypertensive Rats

et al. 2006

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Abstract-NO is implicated as a major modulator of central nervous circuits regulating cardiovascular activity. Based on previous data, we hypothesized that overactivity of endothelial NO synthase (eNOS) within the nucleus tractus solitarii (NTS) could contribute to the hypertension in the spontaneously hypertensive rat (SHR). Using real-time PCR, we found that endogenous eNOS mRNA was greater in the NTS of mature, but not juvenile prehypertensive SHRs compared with aged-matched Wistar Kyoto (WKY) rats. To test the functional significance of this, we chronically blocked eNOS activity in the NTS in the adult SHR by in vivo adenoviral-mediated gene transfer of a dominant-negative form of eNOS; data were compared with WKY rats. This resulted in a fall in arterial pressure in the SHR but not WKY rats. In both rat strains, cardiac baroreceptor reflex gain and the high-frequency spectral component of heart rate variability increased. Thus, endogenous eNOS activity in the NTS plays a major role in determining the set point of arterial pressure in the SHR and contributes to maintaining high arterial blood pressure in this animal model of human hypertension. Key Words: nitric oxide synthase Ⅲ nitric oxide Ⅲ endothelium Ⅲ blood pressure Ⅲ baroreflex Ⅲ sympathetic nervous system Ⅲ neurogenic hypertension A s described by Doba and Reis, 1 destruction of the nucleus tractus solitarii (NTS) leads to fulminating hypertension. This is highly suggestive that the NTS is a central brain stem structure that plays a vital role in maintaining the set point of arterial pressure. Equally, because baroreceptor afferents terminate in this nucleus, it is also one of the most effective central sites for modulating the gain of the baroreceptor reflex, a process that is critically important for blood pressure homeostasis. A potent neuromodulator of central cardiovascular autonomic activity is angiotensin II (Ang II). NTS microinjections of Ang II evoke concentrationdependent effects composed of either a depressor response 2,3 or a pressor/tachycardic response. 4 In addition, an Ang II antagonist increased cardiac baroreceptor reflex gain in anesthetized mature rats. 5 Because of the work of Casto and Philips, 6 it has been known that Ang II acting on Ang II type 1 receptors depresses cardiac baroreceptor reflex function in NTS. We showed that the depressant effect of Ang II type 1 receptor stimulation on cardiac baroreceptor reflex function in the NTS was mediated by NO. 7 We confirmed recently that Ang II can release NO in the NTS using electron paramagnetic resonance. 8 We also found that the effect of Ang II occurs via a Gq-PLC-IP3 pathway that releases intracellular calcium, 9 which we assume is required for activating endothelial NO synthase (eNOS). Released NO enhances inhibitory GABAergic neurotransmission in the NTS, 10 which may underlie the NO-induced cardiac baroreceptor reflex depression. 7 In conscious normotensive Wistar rats, chronic blockade of eNOS activity in NTS elevated the cardiac baroreceptor reflex gain, supporting a de...

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“…Thus, this nucleus plays an important role in the integration of autonomic control of cardiovascular function. Activation of NO-synthesizing neurons distributed throughout the NTS was reported as leading to attenuation of sympathetic nervous activity, to lowering the SAP level, and to a decrease in the heart rate (HR) [59,60]. Similar changes in the SAP were observed following an enhancement of the NO production in other nuclei within the dorsomedial medulla, and patterns of the respective cardiovascular responses were analyzed [61,62].…”

Section: Nitric Oxide and Regulation Of Cardiovascular Functionmentioning

confidence: 99%

Nitric oxide: Involvement in the nervous control of cardiovascular function

Shapoval

2004

Neurophysiology

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Identification of nitric oxide (NO) as a neurotransmitter in the CNS resulted in initiation of numerous studies aimed at elucidating the roles of NO not only at a cellular level, but also in regulation of the activity of specific physiological systems coordinated by the brain. In this lecture, we will discuss the state of current knowledge about cellular events in the brain realized with the involvement of NO, distribution of NO-producing neurons in cerebral structures providing central cardiovascular control, peculiarities of NO production, and mechanisms underlying NO-mediated neuromodulatory effects on cardiovascular function. Activation of the NO system in the lower brainstem modulates a variety of neuronal pathways; NO was shown to induce GABA and glutamate releases within the medulla. The NO system in the brain is activated in the states of homeostatic imbalance, including hypertension and stress.

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Involvement of Nitric Oxide in Cardiorespiratory Regulation in the Nucleus Tractus Solitarii

Cited by 27 publications

References 27 publications

Hypoxia-Induced Changes in Protein S-Nitrosylation in Female Mouse Brainstem

Hypoxia-Induced Changes in Protein S-Nitrosylation in Female Mouse Brainstem

Endothelial NO Synthase Activity in Nucleus Tractus Solitarii Contributes to Hypertension in Spontaneously Hypertensive Rats

Nitric oxide: Involvement in the nervous control of cardiovascular function

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