NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits

Li, Yu Long; Gao, Lie; Zucker, Irving H.; Schultz, Harold D.

doi:10.1016/j.cardiores.2007.04.006

Cited by 109 publications

(118 citation statements)

References 35 publications

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“…Our observation that NADPH oxidase-derived superoxide anion mediates the Ang II-enhanced CB chemoreceptor activity in CHF rabbits (Li et al 2004a) suggests an important interaction between these two signaling pathways. Ang II may contribute to depressed bioavailable NO in the CB by suppressing nNOS gene expression (Kihara et al 1997) and/or increased scavenging of NO through superoxide anion production.…”

Section: Role Of No On Cb Function In Chfmentioning

confidence: 75%

“…*P < 0.05 versus control; #P < 0.05 versus SNAP. (Adapted and reprinted from Li et al 2004a, pages 225 and 226, with permission from the Physiological Society.) A schematic overview of known mechanisms contributing to altered carotid body (CB) chemoreflex function in chronic heart failure (CHF).…”

Section: Discussionmentioning

confidence: 99%

“…AT 1 R activation promotes activation of NADPH oxidase with superoxide anion production (Griendling et al 1994). Our preliminary experiments have shown that mRNA and protein expressions of NADPH oxidase subunits are enhanced in CBs from CHF rabbits, and a NADPH oxidase inhibitor (apocynin) and superoxide dismutase mimetic (tempol) inhibit the effect of Ang II on the sensitivity of I K to acute hypoxia (Li et al 2004a). These results suggest that the NADPH oxidase-superoxide anion pathway may mediate the effects of Ang II in CB glomus cells.…”

Section: Role Of Ang II On K + Currents In Cb Glomus Cells In Chfmentioning

confidence: 93%

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Carotid body function in heart failure

Schultz

2007

Respiratory Physiology & Neurobiology

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In this review, we summarize the present state of knowledge of the functional characteristics of the carotid body (CB) chemoreflex with respect to control of sympathetic nerve activity (SNA) in chronic heart failure (CHF). Evidence from both CHF patients and animal models of CHF has clearly established that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in SNA. This adaptive change derives from altered function at the level of both the afferent and central nervous system (CNS) pathways of the reflex arc. At the level of the CB, an elevation in basal afferent discharge occurs under normoxic conditions in CHF rabbits, and the discharge responsiveness to hypoxia is enhanced. Outward voltage-gated K + currents (I K ) are suppressed in CB glomus cells from CHF rabbits, and their sensitivity to hypoxic inhibition is enhanced. These changes in I K derive partly from downregulation of nitric oxide synthase (NOS) / NO signaling and upregulation of angiotensin II (Ang II) / Ang II receptor (AT 1 R) signaling in glomus cells. At the level of the CNS, interactions of the enhanced input from CB chemoreceptors with altered input from baroreceptor and cardiac afferent pathways and from central Ang II further enhance sympathetic drive. In addition, impaired function of NO in the paraventricular nucleus of the hypothalamus participates in the increased SNA response to CB chemoreceptor activation. These results underscore the principle that multiple mechanisms involving Ang II and NO at the level of both the CB and CNS represent complementary and perhaps redundant adaptive mechanisms to enhance CB chemoreflex function in CHF.

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Section: Role Of No On Cb Function In Chfmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Role Of Ang II On K + Currents In Cb Glomus Cells In Chfmentioning

confidence: 93%

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Carotid body function in heart failure

Schultz

2007

Respiratory Physiology & Neurobiology

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“…35 Similarly, NADPH inhibitors and Tempol normalize the enhanced CB chemoreceptor discharge to hypoxemia and normalize the enhanced sensitivity of KVO 2 channels to hypoxia in CB glomus cells from CHF rabbits. 35 These results suggest that the NADPH oxidase-superoxide anion pathway mediates the effects of Ang II in the CB to enhance hypoxic sensitivity in the CHF state.Despite the potent effects of Ang II-AT 1 R on the sensitivity of the CB to hypoxemia, AT 1 R blockade does not alter chemoreceptor discharge or KVO 2 currents in glomus cells at normoxia in CHF animals. 27,33 Thus, Ang II cannot account for the enhanced chemoreceptor activity under normal resting conditions observed in CHF rabbits.…”

mentioning

confidence: 96%

“…64 Still unresolved is the mechanism by which CIH-induced superoxide anion production increases the sensitivity of CB glomus cells and afferent chemoreceptor activity to hypoxia. Based on our work described above, 35 an inhibitory effect of superoxide anion on KVO 2 channels in glomus cells is possible. Other investigators have demonstrated that endothelin-1 (ET-1) may also be involved in the enhanced CB function with CIH.…”

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confidence: 99%

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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Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

Kumar

Prabhakar

2012

Comprehensive Physiology

465

572

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The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article.

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NADPH oxidase-derived superoxide anion mediates angiotensin II-enhanced carotid body chemoreceptor sensitivity in heart failure rabbits

Cited by 109 publications

References 35 publications

Carotid body function in heart failure

Carotid body function in heart failure

Arterial Chemoreceptors and Sympathetic Nerve Activity

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

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