Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits

Li, Yu Long; Xia, Xiao Hong; Zheng, Hong; Gao, Lie; Li, Yi Fan; Li, Dongmei; Patel, Kaushik P.; Wang, Wei; Schultz, Harold D.

doi:10.1016/j.cardiores.2006.03.017

Cited by 111 publications

(161 citation statements)

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“…During this interval, unpaced left ventricular contractility and ejection fraction decline to levels equivalent to moderate compensated CHF in patients. 24,26,27 Single-unit discharge activity of CB chemoreceptors, both at rest and in response to hypoxia, is similarly enhanced over the same time course (Figure 2A). 25 This increased central input from the CB provides a tonic excitatory influence on sympathetic outflow, because hyperoxia reduces resting RSNA in CHF but not control animals ( Figure 2B).…”

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confidence: 74%

“…27,32 CHF upregulates the Ang II level and the expression of the AT 1 R in the rabbit CB. 27 Systemic administration of Ang II in conscious rabbits (to levels equivalent to the endogenous plasma Ang II level in CHF rabbits) enhances hypoxia-induced chemoreflex activation of sympathetic outflow. 27 Furthermore, blockade of AT 1 R in CHF rabbits attenuates (ie, normalizes) the exaggerated hypoxia-induced chemoreflex responses observed in CHF rabbits.…”

Section: Schultz Et Al Chemoreflex and Sympathetic Nerve Activitymentioning

confidence: 99%

“…27,33 Thus, Ang II cannot account for the enhanced chemoreceptor activity under normal resting conditions observed in CHF rabbits. [25][26][27] Other evidence suggests that downregulation of an NO mechanism is likely to participate in the enhanced basal activity in the CB in CHF. 25,26 Both neuronal NO synthase (nNOS; NOS) and endothelial NOS are present in the CB, and NO is inhibitory to CB activity.…”

Section: Schultz Et Al Chemoreflex and Sympathetic Nerve Activitymentioning

confidence: 99%

“…27 Afferent recordings from the isolated CB confirm that elevation of Ang II and AT 1 R in the CB enhances chemoreceptor sensitivity to hypoxemia in CHF rabbits. 27 The mechanism by which Ang II enhances the hypoxic sensitivity of the CB chemoreceptors involves an interaction with oxygen sensitive, voltage-gated potassium channels (KVO 2 ) in CB glomus cells. 33 Hypoxic inhibition of KVO 2 channels is enhanced in isolated CB glomus cells from CHF rabbits, and blockade of AT 1 R alone is capable of reversing this enhanced hypoxic sensitivity.…”

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Arterial Chemoreceptors and Sympathetic Nerve Activity

2007

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C hronic elevation in sympathetic nerve activity (SNA) is associated with the development and maintenance of certain types of hypertension 1 and contributes to the progression of chronic heart failure (CHF). 2 The mechanisms involved in sympathetic dysfunction in these disorders appear to be complex and multifactorial. A unified hypothesis is likely to encompass alterations in multiple autonomic reflex pathways, central integratory sites, and chemical mediators that control sympathetic outflow. For example, tonic restraint of sympathetic outflow by arterial and cardiopulmonary baroreflexes is depressed in CHF 2 and depressed or reset in hypertension. 3 Moreover, maladaptive changes also occur in the central nervous system at integrative sites for autonomic control in both disease processes. 4,5 It is also clear that sympathoexcitatory cardiac, 6 somatic, 7 and central/peripheral chemoreceptor reflexes 8 are enhanced in CHF and hypertension.Arterial chemoreceptors serve an important regulatory role in the control of alveolar ventilation, but they also exert a powerful influence on cardiovascular function. 9 Activation of arterial chemoreceptors by hypoxemia increases sympathetic outflow to systemic vascular beds to compensate for the direct vasodilating effects of hypoxia on these vessels and to redistribute blood flow to essential organs. In this review, we highlight relevant information that implicates the arterial chemoreflex as a contributory mechanism for the sympathetic hyperactivity in CHF and hypertension and illustrate proposed mechanisms for this altered function. The Sympathetic Response to Arterial Chemoreceptor ActivationArterial chemoreceptors located in the aortic and carotid bodies (CBs) respond to hypoxemia and hypercapnia. Because central chemoreceptors also respond to hypercapnia, hypoxia is typically used as a specific stimulus to arterial chemoreceptors. In some mammals, such as rats and rabbits, reflex responses to hypoxemia arise solely from the CB, whereas in other species, the aortic chemoreceptor contribution can be significant. However, it is not possible to experimentally separate the relative contribution of the aortic and CBs to reflex responses in conscious animals or humans. For these reasons, discussions on the arterial chemoreflex generally relate functionality to that of the CB, which has been more extensively studied. Glomus cells in the CB depolarize in response to hypoxia and release multiple putative neurotransmitters (including acetylcholine, serotonin, ATP, and substance P) that activate impulses in afferent fibers traveling to the medulla via the carotid sinus nerve. 10 Arterial chemoreceptor stimulation in freely breathing humans and conscious animals increases sympathetic vasoconstrictor outflow to muscle, splanchnic, and renal beds to elevate arterial pressure, and, in humans, increases cardiac sympathetic activity to increase heart rate and contractility. 9 There is preferential activation of sympathetic fibers going to the adrenal gland to increase norepinephrine but...

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confidence: 74%

Section: Schultz Et Al Chemoreflex and Sympathetic Nerve Activitymentioning

confidence: 99%

Section: Schultz Et Al Chemoreflex and Sympathetic Nerve Activitymentioning

confidence: 99%

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confidence: 99%

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Arterial Chemoreceptors and Sympathetic Nerve Activity

2007

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“…Antagonism of ANG II reduces sympathetic outflow and effectively normalizes cardiovascular reflexes in CHF (7,14,19). The blockade of ANG II type 1 receptors (AT 1 Rs) in the brain attenuates the increased sympathetic activity and restores the blunting of baroreflex induced by activation of the CSAR, suggesting that the ANG II system in the central nervous system may be a major mechanism responsible for CSAR-induced cardiovascular effects (13,15).…”

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confidence: 99%

Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT₁ receptors in heart failure

Wang¹,

Gao²,

Wang³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT 1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT 1R antagonist losartan (10 and 100 pmol) dosedependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSARinduced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT 1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT 1R-dependent mechanism. sympathoexcitatory reflexes; sympathetic activity; angiotensin II type 1 receptor; microinjection; extracellular recording; nucleus of tractus solitarius THE ELEVATED SYMPATHETIC OUTFLOW in the chronic heart failure (CHF) has long been known to be closely associated with the accelerated progression and the poor prognosis of this syndrome (6, 9). The sympathetic hyperactivity is closely related to abnormalities in cardiovascular reflexes in CHF. Sympathoinhibitory cardiovascular reflexes such as the arterial baroreceptor reflex are significantly suppressed in CHF (21, 38). On the other hand, the sympathoexcitatory reflexes including the arterial chemoreceptor reflex and the cardiac sympathetic afferent reflex (CSAR) are exaggerated in CHF (34, 39). Although functional alterations of the above-mentioned reflexes have been independently used to illustrate the sympathoexcitation observed in CHF, the interaction among these reflexes in both the normal and CHF conditions, especially on their contributions to the sympathoexcitatory state in CHF, has been not extensively studied.In CHF, a variety of substances, such as bradykinin, that are released by the myocardium during ischemia can effectively stimulate the cardiac sympathetic afferents and subsequently increase sympathetic outflow (24...

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Historical Perspectives on the Control of Breathing

Fitzgerald

Cherniack

2012

Comprehensive Physiology

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Among the several topics included in respiratory studies investigators have focused on the control of breathing for a relatively few number of years, perhaps only the last 75 to 80. For a very long time, the phenomenon of respiration presented a great mystery. The Chinese had suggestions for proper breathing, and later the Egyptians sought to understand its purpose. But in the western world, the early Greeks made the more significant observations. Centuries passed before the anatomical structures pertinent to respiration were properly visualized and located. There followed efforts to understand if lung movement was necessary for life and what happened in the lung. The rise of chemistry in the 18th century eventually clarified the roles of the gases significant in respiratory behavior. More time was needed to understand what gases provoked increases in breathing and where those gases worked. At this point, control of breathing became a significant focus of respiratory investigators. Studies included identifying the structures and functions of central and peripheral chemoreceptors, and airway receptors, sources of respiratory rhythm and pattern generation, the impact of the organism's status on its breathing including environment and disease/trauma. At this same time, mid- to late-20th century, efforts to mathematicize the variables in the control of breathing appeared. So though wonderment about the mysterious phenomenon of respiration began over two millennia ago, serious physiological investigation into its control is by comparison very young.

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Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits

Abstract: These results indicate that elevation of Ang II and concomitant upregulation of AT1 receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.

Cited by 111 publications

References 26 publications

Arterial Chemoreceptors and Sympathetic Nerve Activity

Arterial Chemoreceptors and Sympathetic Nerve Activity

Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT₁ receptors in heart failure

Historical Perspectives on the Control of Breathing

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Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits

Abstract: These results indicate that elevation of Ang II and concomitant upregulation of AT1 receptor in the CB contribute to the increased CB chemoreceptor activity and enhanced peripheral chemoreflex function in CHF.

Cited by 111 publications

References 26 publications

Arterial Chemoreceptors and Sympathetic Nerve Activity

Arterial Chemoreceptors and Sympathetic Nerve Activity

Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure

Historical Perspectives on the Control of Breathing

Contact Info

Product

Resources

About

Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT₁ receptors in heart failure