Ablation of NK1 Receptors in Rat Nucleus Tractus Solitarii Blocks Baroreflexes

Riley, Jeffrey B.; Lin, Leou-Chyr; Chianca, Deoclécio A.; Talman, William T.

doi:10.1161/01.hyp.0000042089.34004.cf

Cited by 27 publications

(43 citation statements)

References 28 publications

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“…We show that selectively destroying NK1 receptor neurons in the NTS leads to chronic lability of arterial pressure, a finding consistent with loss of baroreflex responses (4,24). Although an earlier paper (1) showed a recording of arterial pressure that suggested the presence of lability after damage to NTS neurons with NK1 receptors, our observation is the first to our knowledge to document with data analysis that lability does develop and mimics that seen with less selective NTS lesions (32).…”

Section: Discussionsupporting

confidence: 77%

“…Immunofluorescent and immunohistochemical analysis of the brain stem performed 10 -12 days after unilateral injections of SSP-SAP into NTS revealed reduction in NK1 neuronal staining in the NTS only on the side of injection as had been seen previously when substance P (SP)-SAP, rather than SSP-SAP had been injected (24). As shown in Fig.…”

Section: Effects Of Ssp-sap On Nts Neurons With Nk1 Receptorssupporting

confidence: 61%

“…MAP was sampled for 10 s every minute for 10 -12 days. This shorter period of recording than was used in our previous study (24) reflected our efforts to reduce the incidence of sudden death. ECG waveforms were sampled for 10-s intervals every 30 s at a rate of 500 Hz.…”

Section: Methodsmentioning

confidence: 90%

“…In an earlier study, we injected into NTS a toxin that selectively targeted neurons with NK1 receptors (24), and we showed that the ensuing lesion attenuated baroreflex responses (24). The altered baroreflex transmission was associated with sudden, unexpected, death in 33% of the experimental animals.…”

mentioning

confidence: 84%

“…For chromogen-based immunohistochemistry, we followed methods described previously (24). In three animals, SSP-SAP was injected unilaterally to provide comparison between the side with a lesion and the contralateral side that served as an intra-animal control.…”

Section: Methodsmentioning

confidence: 99%

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Cardiac damage after lesions of the nucleus tractus solitarii

Nayate

Moore²,

Weiss³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Nayate A, Moore SA, Weiss R, Taktakishvili OM, Lin L.-H., Talman WT. Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 296: R272-R279, 2009. First published November 19, 2008 doi:10.1152/ajpregu.00080.2008.-Humans with central lesions that augment sympathetic nerve activity are predisposed to cardiac arrhythmias, myocardial lesions, and sudden death. Previously, we showed that selectively killing neurons with neurokinin-1 receptors in the nucleus tractus solitarii (NTS) of rats attenuated the baroreflex and, in some animals, led to sudden unexplained death within ϳ2 wk. Interruption of arterial baroreflexes is known to increase sympathetic activity. Here we tested the hypothesis that lesions in the NTS lead to fatal cardiac arrhythmias and myocardial lesions. We studied electrocardiograms, echocardiograms, blood pressure, and heart rate in 14 adult male rats after bilateral microinjection into the NTS of stabilized substance P conjugated to the toxin saporin and compared the variables in five sham control rats and in five animals with toxin injected outside the NTS. Only injection of toxin into the NTS led to increased lability of arterial blood pressure, a sign of baroreflex interruption. Two animals treated with toxin died suddenly. All animals engaged in normal activity until, in two, rapid development of asystole and death over 6 -8 min. Cardiac function when examined by echocardiography was normal, but pathologic examination of the heart revealed diffuse microscopic areas of acute coagulation necrosis in the myocardium in five animals, focal subacute necrosis in two animals, and both changes in one animal. This study supports the hypothesis that NTS lesions interrupting the baroreflex may induce cardiac arrhythmias and myocardial changes similar to those seen in humans with central lesions and may lead to sudden cardiac death. baroreflex; cardiac arrhythmia; heart injuries; sudden death; sympathetic nervous system PREVIOUS STUDIES HAVE SUGGESTED that substance P, acting at neurons that express neurokinin-1 (NK1) receptors, may participate in transmission of arterial baroreflexes at the level of the nucleus tractus solitarii (NTS) (17,23,26). In an earlier study, we injected into NTS a toxin that selectively targeted neurons with NK1 receptors (24), and we showed that the ensuing lesion attenuated baroreflex responses (24). The altered baroreflex transmission was associated with sudden, unexpected, death in 33% of the experimental animals. Death in these animals was reminiscent of that seen in humans who have sustained central lesions (30). While subarachnoid hemorrhage is a most common cause, other central lesions that lead to enhanced sympathetic nerve activity also predispose an individual to the fatal outcome (30). In fact, sympathetic nerve activity and excessive circulating catecholamines alone may lead to cardiac arrhythmias and death (12,33). Sudden death in humans with central lesions correlates with cardiac arrhythmias, but the lesions also may l...

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Section: Discussionsupporting

confidence: 77%

Section: Effects Of Ssp-sap On Nts Neurons With Nk1 Receptorssupporting

confidence: 61%

Section: Methodsmentioning

confidence: 90%

mentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

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Cardiac damage after lesions of the nucleus tractus solitarii

Nayate

Moore²,

Weiss³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

et al. 2012

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Lesions that remove neurons expressing neurokinin-1 (NK1) receptors from the nucleus tractus solitarii (NTS) without removing catecholaminergic neurons lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) may also cause lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions associated with lability are not dependent on damage to neurons with NK1 receptors but would also occur when TH neurons in NTS are targeted. To rid the NTS of TH neurons we microinjected anti-dopamine β-hydroxylase conjugated to saporin (anti-DBH-SAP, 42ng/200nl) into the NTS. After injection of the toxin unilaterally, immunofluorescent staining confirmed that anti-DBH-SAP decreased the number of neurons and fibers that contain TH and DBH in the injected side of the NTS while sparing neuronal elements expressing NK1 receptors. Bilateral injections in 8 rats led to significant lability of arterial pressure. For example, on day 8 standard deviation of mean arterial pressure was 16.8 ± 2.5 mmHg when compared with a standard deviation of 7.83 ± 0.33 mmHg in 6 rats in which phosphate buffered saline (PBS) had been injected bilaterally. Two rats died suddenly at 5 and 8 days after anti-DBH-SAP injection. Seven treated animals demonstrated microscopic myocardial necrosis as reported in animals with lesions of NTS neurons expressing NK1 receptors. Thus, cardiac and cardiovascular effects of lesions directed toward catecholamine neurons of the NTS are similar to those following damage directed toward NK1 receptor containing neurons.

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Substance P in the cardiovascular system

Chottova Dvorakova,

Pandey

2025

Substance P

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Ablation of NK1 Receptors in Rat Nucleus Tractus Solitarii Blocks Baroreflexes

Cited by 27 publications

References 28 publications

Cardiac damage after lesions of the nucleus tractus solitarii

Cardiac damage after lesions of the nucleus tractus solitarii

Sudden Death and Myocardial Lesions after Damage to Catecholamine Neurons of the Nucleus Tractus Solitarii in Rat

Substance P in the cardiovascular system

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