Landmarks in understanding the central nervous control of the cardiovascular system

Coote, John H.

doi:10.1113/expphysiol.2006.035378

Cited by 77 publications

(63 citation statements)

References 170 publications

(235 reference statements)

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“…Based on the available information regarding medullo-spinal cardiovascular regulatory areas (Coote, 2007;Gordon and Sved, 2002;Guyenet, 2006;Sapru, 2002Sapru, , 2004Talman et al, 1984), the following mechanism may be involved in mediating the cardiovascular responses elicited by MCH microinjections into the mNTS. MCH stimulates mNTS neurons as shown by direct pressure micro-applications of this peptide to these neurons.…”

Section: Discussionmentioning

confidence: 99%

“…The nucleus tractus solitarius (NTS) is one of the medullary structures that plays an important role in the central regulation of cardiovascular function (for reviews see: Coote, 2007;Gordon and Sved, 2002;Guyenet, 2006;Sapru, 2002Sapru, , 2004Talman et al, 1984). The presence of MCH containing fibers and MCH-1 receptors has been demonstrated in the NTS (Hervieu et al, 2000;Zamir et al, 1986a,b).…”

Section: Introductionmentioning

confidence: 99%

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Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

et al. 2007

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The presence of melanin-concentrating hormone (MCH) containing processes, projecting from the lateral hypothalamus to the medial nucleus tractus solitarius (mNTS), has been reported in the rat. It was hypothesized that MCH acting within the mNTS may modulate the central regulation of cardiovascular function. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of MCH (0.25, 0.5, 0.75, and 1 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (20.4 ± 1.6, 50.7 ± 3.3, 35.7 ± 2.8 and 30.0 ± 2.6 mmHg, respectively). The decreases in heart rate in response to these concentrations of MCH were 40.0 ± 8.7, 90.0 ± 13.0, 48.0 ± 7.3 and 48.0 ± 8.0 beats/min, respectively. Maximum cardiovascular responses were elicited by a 0.5 mM concentration of MCH. Cardiovascular responses to MCH were similar in unanesthetized mid-collicular decerebrate rats. Control microinjections of normal saline (100 nl) did not elicit any cardiovascular response. Ipsilateral or bilateral vagotomy significantly attenuated MCH-induced bradycardia. Prior microinjections of PMC-3881-PI (2 mM; MCH-1 receptor antagonist) into the mNTS blocked the cardiovascular responses to microinjections of MCH. Microinjection of MCH (0.5 mM) into the mNTS decreased efferent greater splanchnic nerve activity. Direct application of MCH (0.5 mM; 4 nl) to barosensitive NTS neurons increased their firing rate. These results indicate that: 1) MCH microinjections into the mNTS activate MCH-1 receptors and excite barosensitive NTS neurons, causing a decrease in efferent sympathetic activity and blood pressure, and 2) MCH-induced bradycardia is mediated via the activation of the vagus nerves.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

et al. 2007

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“…[22][23][24][25][26][27] Importantly, it also receives the inputs from the paraventricular nucleus of the hypothalamus, which is known as a key nucleus of the central cardiovascular regulation. 22,28,29 Therefore, we focused on the RVLM in our studies. Other investigators have also confirmed our initial observations, and other details have been further investigated.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

Hirooka

2011

Hypertens Res

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Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension Yoshitaka HirookaActivation of the sympathetic nervous system has an important role in the pathogenesis of hypertension. However, the precise mechanisms involved are not fully understood. Oxidative stress may be important in hypertension as well as in other cardiovascular disorders. We investigated the role of oxidative stress, particularly in the rostral ventrolateral medulla (RVLM), which is known as the cardiovascular center in the brainstem, in the activation of the sympathetic nervous system in hypertension. We observed that the reactive oxygen species (ROS) production increases in the RVLM in hypertensive rats, thereby enhancing the central sympathetic outflow, which leads to hypertension. Furthermore, the environmental factors of high salt intake and a high-calorie diet may also increase the ROS production in the RVLM, thereby activating the central sympathetic outflow and increasing the risk of hypertension. The activation of the nicotinamide adenine dinucleotide phosphate oxidase via the angiotensin type 1 (AT1) receptors is suggested to be the major source of ROS production, and an altered downstream signaling pathway is involved in the activation of the RVLM neurons, leading to enhanced central sympathetic outflow and hypertension. Thus, the brain AT1 receptors may be novel therapeutic targets, and, in fact, oral treatment with angiotensin receptor blockers has been found to inhibit the central AT1 receptors, despite the blood-brain barrier.

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“…Key Words: cardiovascular control Ⅲ GABA Ⅲ substance P T he parvocellular subdivision of the hypothalamic paraventricular nucleus (PVN) contains both hypothalamicpituitary-adrenal axis control neurons, and spinally-projecting cardiovascular control neurons. [1][2][3][4][5][6] Estimates suggest that up to 2000 neurons project directly from the PVN to the intermediolateralis (IML) of the spinal cord. 7-9 These projecting parvocellular neurons have been implicated in a number of facets of cardiovascular control.…”

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confidence: 99%

Substance P Targets Sympathetic Control Neurons in the Paraventricular Nucleus

Womack

Morris

Gent

et al. 2007

Circulation Research

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Abstract-The paraventricular nucleus (PVN) contains spinally-projecting neurons implicated in fine-tuning the cardiovascular system. In vivo activity of "presympathetic" parvocellular neurons is suppressed by tonic inhibition from GABA-ergic inputs, inhibition of which increases sympathetic pressor activity and heart rate. Targeting of this specific neuronal population could potentially limit elevations of heart rate and blood pressure associated with disease. Here we show, for the first time, that "presympathetic" PVN neurons are disinhibited by the neuropeptide substance P (SP) acting via tachykinin NK1 receptor inhibition of GABA A currents. Application of SP to the paraventricular nucleus of rats increases heart rate and blood pressure. Key Words: cardiovascular control Ⅲ GABA Ⅲ substance P T he parvocellular subdivision of the hypothalamic paraventricular nucleus (PVN) contains both hypothalamicpituitary-adrenal axis control neurons, and spinally-projecting cardiovascular control neurons. [1][2][3][4][5][6] Estimates suggest that up to 2000 neurons project directly from the PVN to the intermediolateralis (IML) of the spinal cord. 7-9 These projecting parvocellular neurons have been implicated in a number of facets of cardiovascular control. For example, circadian regulation of blood pressure, 10 blood-volume regulation, 7,8 and the cardiovascular response to psychological stress. 11 Furthermore, elevated sympathetic activity is associated with congestive heart failure observed in humans and animals, 12-14 and rat models suggest that this is associated with a diminished GABA sensitivity of PVN neurons. 13,15,16 As such, spinally-projecting PVN neurons are prime targets for therapeutic intervention with the cardiovascular system.Although there have been, to date, few in vitro studies detailing cellular mechanisms potentially exploitable for therapeutic control of cardiovascular PVN neurons, there have been a number of, largely in vivo, studies investigating their basic control and physiological activity. Early in vivo electrophysiological studies on cats confirmed an anticipated monosynaptic connection between the PVN and spinal sympathetic motor area (the IML). 17 Furthermore, stimulation (electrical or glutamate) of the PVN was shown to give rise to an extremely rapid rise of blood pressure and renal sympathetic outflow in conscious rats. 18 Additional studies show that in vivo, the PVN receives tonic inhibition from GABAergic inputs and this maintains their activity at relatively low levels, 19 -21 despite the fact that these neurons also receive excitatory glutaminergic inputs. 18 Strikingly, excitation of this nucleus by glutamate, or by blockade of GABA A receptors with the antagonist bicuculline, increases blood pressure and heart rate. 18,22 Other physiological inputs to "presympathetic" parvocellular neurons have been, until now, unknown. Potentially, pharmacological inhibition of this neuronal population could limit sympathetically induced elevations of heart rate and blood pressure seen during hea...

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Landmarks in understanding the central nervous control of the cardiovascular system

Cited by 77 publications

References 170 publications

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

Microinjections of melanin concentrating hormone into the nucleus tractus solitarius of the rat elicit depressor and bradycardic responses

Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension

Substance P Targets Sympathetic Control Neurons in the Paraventricular Nucleus

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