Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus

Fontes, Marco Antônio Peliky; Tagawa, Tatsuya; Polson, Jaimie W.; Cavanagh, S.-J.; Dampney, R.A.L.

doi:10.1152/ajpheart.2001.280.6.h2891

Cited by 169 publications

(190 citation statements)

References 33 publications

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“…Yet another explanation is that C1 adrenergic neurons were firing at a higher rate in lactate + L-AG-treated rats, relative to lactate + D-AG-treated rats, even though lactate induced a similar level of c-Fos expression in C1 adrenergic neurons in the RVLM similarly in both D-AG and L-AG-treated rats challenged with lactate. Consistent with a role for the RVLM/C1 adrenergic cell groups in DMH/PeF-mediated cardiovascular responses, pressor responses, elicited from disinhibition of the DMH, can be severely attenuated by microinjecting muscimol into the RVLM (Fontes et al, 2001). Tachycardia responses following L-AG + lactate infusions are most likely being mobilized by a combination of direct and indirect projections from the DMH/PeF to sympathetic preganglionic neurons.…”

Section: Pathways For Lactate-induced Panic-like Responsesmentioning

confidence: 68%

“…However, increased c-Fos responses in the DMM were not occurring in parasympathetic preganglionic acetylcholinergic neurons (DMV and Amb), or other regions involved in the baroreflex-mediated sympathetic inhibition (eg CVLM) (Chan and Sawchenko, 1998). The DMH directly innervates the nTS (Fontes et al, 2001), and electrical or chemical (see review (McDowall et al, 2006)) stimulation of the DMH decreases the sensitivity of the baroreflex through a GABAergic mechanism in the nTS/DMV (Jordan et al, 1988). This circuit represents an adaptive means of inhibiting the baroreflex during 'fight or flight' responses and exercise (Potts et al, 2003).…”

Section: Pathways For Lactate-induced Panic-like Responsesmentioning

confidence: 96%

“…Since evidence from previous studies suggested that disinhibiting the DMH elicits cardioexcitatory responses by mobilizing sympathetic outflow (see review (DiMicco et al, 2002)) and resetting the sensitivity of the baroreflex, which is parasympathetically mediated (see review McDowall et al, 2006), we hypothesized that disinhibition of the DMH/PeF alters lactate-induced behavioral, respiratory, and cardiovascular responses through efferent targets involved in central sympathetic and parasympathetic autonomic control (Dampney, 1994;Thompson and Swanson, 1998;Fontes et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Neural Pathways Underlying Lactate-Induced Panic

Johnson

Truitt

Fitz

et al. 2007

Neuropsychopharmacol

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Panic disorder is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as 0.5 M sodium lactate infusions. Although studied for four decades, the mechanism of lactate sensitivity in panic disorder has not been understood. The dorsomedial hypothalamus/perifornical region (DMH/PeF) coordinates rapid mobilization of behavioral, autonomic, respiratory and endocrine responses to stress, and rats with disrupted GABA inhibition in the DMH/PeF exhibit panic-like responses to lactate, similar to panic disorder patients. Utilizing a variety of anatomical and pharmacological methods, we provide evidence that lactate, via osmosensitive periventricular pathways, activates neurons in the compromised DMH/PeF, which relays this signal to forebrain limbic structures such as the bed nucleus of the stria terminalis to mediate anxiety responses, and specific brainstem sympathetic and parasympathetic pathways to mediate the respiratory and cardiovascular components of the panic-like response. Acutely restoring local GABAergic tone in the DMH/PeF blocked lactate-induced panic-like responses. Autonomic panic-like responses appear to be a result of DMH/PeF-mediated mobilization of sympathetic responses (verified with atenolol) and resetting of the parasympathetically mediated baroreflex. Based on our findings, DMH/PeF efferent targets such as the C1 adrenergic neurons, paraventricular hypothalamus, and the central amygdala are implicated in sympathetic mobilization; the nucleus of the solitary tract is implicated in baroreflex resetting; and the parabrachial nucleus is implicated in respiratory responses. These results elucidate neural circuits underlying lactate-induced panic-like responses and the involvement of both sympathetic and parasympathetic systems.

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Section: Pathways For Lactate-induced Panic-like Responsesmentioning

confidence: 68%

Section: Pathways For Lactate-induced Panic-like Responsesmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Neural Pathways Underlying Lactate-Induced Panic

Johnson

Truitt

Fitz

et al. 2007

Neuropsychopharmacol

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“…The present experiments were performed in anesthetized animals because this model has the advantage of minimizing the cardiovascular variability observed in conscious animals, caused by stress that may interfere with the central mechanisms involved in the reflex cardiovascular changes (Golin et al, 1991;Fontes et al, 2001;Dampney et al, 2002). In addition, urethane anesthesia is more suitable for experiments in which autonomic reflex compensatory changes are involved (Shimokawa et al, 1998), such as tilting experiments (Miki et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Evidence for a functional cardiac interaction between losartan and angiotensin‐(1–7) receptors revealed by orthostatic tilting test in rats

Moura¹,

Santos²,

Fontes³

2005

British J Pharmacology

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1 Studies have shown that the angiotensin II (Ang II) AT 1 receptor antagonist, losartan, accentuates the orthostatic hypotensive response in anesthetized rats, and there is evidence indicating that this effect is not exclusively mediated by AT 1 receptors. 2 We investigated whether the pronounced orthostatic cardiovascular response observed in losartantreated rats involves an interference with angiotensin-(1-7) (Ang-(1-7)) receptors. 3 Urethane-anesthetized rats were submitted to orthostatic stress (901 head-up tilt for 2 min). Intravenous injection of losartan (1 mg kg À1 , n ¼ 9) significantly accentuated the decrease in mean arterial pressure (MAP) induced by head-up tilt (À3376% after losartan vs À1578% control tilt). This effect was accompanied by a significant bradycardia (À873% after losartan vs À373% control tilt). Another AT 1 antagonist, candesartan, did not potentiate the decrease of MAP and did not change the cardiac response induced by head-up tilt. Strikingly, administration of the Ang-(1-7) antagonist, A-779 (10 nmol kg À1 , n ¼ 5), totally reversed the bradicardiac effect caused by losartan and this effect was accompanied by a tendency towards attenuation of the hypotensive response caused by losartan. 4 These findings indicate that the marked orthostatic cardiovascular response is specific for losartan, and that it may be due, in part, to an interaction of this antagonist with Ang-(1-7) receptors, probably at the cardiac level.

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“…There are data demonstrating that the central pathways mediating the increased sympathetic vasomotor activity could, at least in part, be separated from the pathways mediating the tachycardia. 33 …”

Section: Influence Of Npy Upregulation On Blood Pressurementioning

confidence: 99%

Hypotension and Reduced Catecholamines in Neuropeptide Y Transgenic Rats

et al. 2003

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Abstract-The neurons that control blood pressure express neuropeptide Y. Administered centrally, this neuropeptide reduces blood pressure and anxiety, together with lowering sympathetic outflow. The generation of neuropeptide Y transgenic rats overexpressing this peptide, under its natural promoter, has allowed us to examine the role of endogenous neuropeptide Y in the long-term control of blood pressure by the sympathetic nervous system. This study tested a hypothesis that endogenous neuropeptide Y acts to reduce blood pressure and catecholamine release. Blood pressure was measured by radiotelemetry in conscious male transgenic and nontransgenic littermates (control). Novel cage with cold water and forced swimming were used as stressors. Catecholamines were determined in 24-hour urine (baseline) and plasma (cold water stress) by a radioenzymatic assay. Blood pressures in baseline and during the stresses were significantly reduced in the transgenic rats. The lower blood pressure was associated with reduced catecholamines, lower decrease in pressure after autonomic ganglionic blockade, and increased longevity. Data obtained through the use of this transgenic rat model support and extend the evidence for the previously postulated sympatholytic and hypotensive effects of neuropeptide Y and provide novel evidence for an important physiological role of endogenous peptide in blood pressure regulation. As indicated by the increased longevity of these rats, in long-term regulation, these buffering actions of neuropeptide Y may have important cardiovascular protective effects against sympathetic hyperexcitation. Key Words: hypotension Ⅲ nervous system, sympathetic renal Ⅲ stress Ⅲ sympatholytics Ⅲ catecholamines Ⅲ rats, transgenic T he neurons involved in blood pressure regulation express high quantities of neuropeptide Y (NPY). In the central nervous system, a high degree of NPY expression is present, particularly in the paraventricular nucleus of the hypothalamus, ventrolateral medulla, nucleus of tractus solitari, and in the bulbospinal neurons. [1][2][3][4][5] In the peripheral organs, NPY is expressed in sympathetic neurons innervating arteries and veins. 6,7 A remarkable feature of this peptide is its close coexistence and corelease with norepinephrine. 5-8 Exogenous NPY exerts either a hypertensive or a hypotensive effect, depending on the site of its administration. Administered centrally, the peptide has potent sympatholytic, hypotensive, and anxiolytic effects. 9 -13 In contrast, acute administration of NPY into the systemic circulation increases blood pressure. 6 Altogether, the accumulated data indicate that endogenous NPY is an important transmitter of the sympathetic nervous system involved in regulation of blood pressure. However, because of its broad distribution in the nervous system, the complexity of signaling (which involves at least 5 different receptors), the peptide interaction with other neurotransmitters, and the lack of specific antagonists, it is difficult to understand the factual physiologic...

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Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus

Cited by 169 publications

References 33 publications

Neural Pathways Underlying Lactate-Induced Panic

Neural Pathways Underlying Lactate-Induced Panic

Evidence for a functional cardiac interaction between losartan and angiotensin‐(1–7) receptors revealed by orthostatic tilting test in rats

Hypotension and Reduced Catecholamines in Neuropeptide Y Transgenic Rats

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