Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure

Despas, Fabien; Lambert, Elisabeth; Vaccaro, Angelica; Labrunée, M.; Franchitto, Nicolas; Lebrin, Marine; Galinier, Michel; Senard, Jean‐Michel; Lambert, Gavin; Esler, Murray; Pathak, Atul

doi:10.1097/hjh.0b013e328350136c

Cited by 74 publications

(67 citation statements)

References 35 publications

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“…Augmented peripheral chemoreflex control of sympathetic nerve activity during hypoxia has been documented in pacing-induced HF in rabbits 24 and humans with HF. 6,25 More recently, other investigators reported that increased chemoreflex sensitivity decreases baroreflex control of sympathetic nerve activity in chronic HF patients, 26 which may explain the role of the chemoreflex sensitivity in the adverse prognosis in ambulatory patients with chronic HF. 27 The novel finding in the present study is the increased peripheral chemoreflex control of MSNA even in very mild change in oxygen saturation (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

et al. 2012

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Abstract-We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O 2 and 90% N 2 ). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N G -monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012;60:669-676.) • Online Data Supplement Key Words: heart failure � chemoreceptors � vasodilation � sympathetic nervous system � endothelium R esting sympathetic nerve activity is increased in patients with chronic systolic heart failure (HF), and patients with the greatest sympathetic activation have the highest mortality.1,2 Many potential mechanisms underlying the sympathetic excitation in HF have been proposed, including blunted baroreceptor control of central sympathetic outflow.3,4 Augmented peripheral chemoreceptor sensitivity in HF has also been described, which may also underlie the augmented central sympathetic outflow. 5,6 In healthy humans, hypoxia leads to increased blood flow directed to skeletal muscle, and this vasodilatation is mediated by NO release. 7 In a recent study, we reported that, paradoxically, the peripheral chemoreceptor stimulation resulted in skeletal muscle vasoconstriction in HF patients. 6 This unexpected vascular response led us to hypothesize that either the exaggerated sympathetic outflow attributable to chemoreceptor stimulation or the blunted endothelially mediated vasodilatation results in this muscle vasoconstriction during hypoxia in HF patients. In the present study, we describe muscle blood flow responses during peripheral chemoreceptor stimulation with local blockade of postsynaptic ␣-adrenergic receptors and in association with blockade of endothelial NO production in patients with severe HF and in healthy controls. In addition, we describe the effects of vitamin C, an antioxidant, alone, and an ant...

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

et al. 2012

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“…For instance, activation of CSAR depresses ABR and enhances the arterial chemoreflex via central integration (Du and Chen, 2006; Chen et al, 2015) (Figure 3A). The afferent pathways of these reflex mechanisms project to the NTS, and numerous lines of investigation attests that baroreflex dysfunction of the MSNA is the consequence of and not the cause of the reflex sympathetic excitation seen in HF patients (Du and Chen, 2006; Despas et al, 2012) (Figure 3B). In this regard, an experimental study showed that electrical stimulation of the central end of the left cardiac sympathetic nerve blunts ABR sensitivity by 42% (Figure 3A), and this effect is abolished after intra-cerebroventricular injection of losartan (Gao et al, 2004).…”

Section: Hyperadrenergic State In Heart Failurementioning

confidence: 99%

Contribution of Autonomic Reflexes to the Hyperadrenergic State in Heart Failure

et al. 2017

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Heart failure (HF) is a complex syndrome representing the clinical endpoint of many cardiovascular diseases of different etiology. Given its prevalence, incidence and social impact, a better understanding of HF pathophysiology is paramount to implement more effective anti-HF therapies. Based on left ventricle (LV) performance, HF is currently classified as follows: (1) with reduced ejection fraction (HFrEF); (2) with mid-range EF (HFmrEF); and (3) with preserved EF (HFpEF). A central tenet of HFrEF pathophysiology is adrenergic hyperactivity, featuring increased sympathetic nerve discharge and a progressive loss of rhythmical sympathetic oscillations. The role of reflex mechanisms in sustaining adrenergic abnormalities during HFrEF is increasingly well appreciated and delineated. However, the same cannot be said for patients affected by HFpEF or HFmrEF, whom also present with autonomic dysfunction. Neural mechanisms of cardiovascular regulation act as “controller units,” detecting and adjusting for changes in arterial blood pressure, blood volume, and arterial concentrations of oxygen, carbon dioxide and pH, as well as for humoral factors eventually released after myocardial (or other tissue) ischemia. They do so on a beat-to-beat basis. The central dynamic integration of all these afferent signals ensures homeostasis, at rest and during states of physiological or pathophysiological stress. Thus, the net result of information gathered by each controller unit is transmitted by the autonomic branch using two different codes: intensity and rhythm of sympathetic discharges. The main scope of the present article is to (i) review the key neural mechanisms involved in cardiovascular regulation; (ii) discuss how their dysfunction accounts for the hyperadrenergic state present in certain forms of HF; and (iii) summarize how sympathetic efferent traffic reveal central integration among autonomic mechanisms under physiological and pathological conditions, with a special emphasis on pathophysiological characteristics of HF.

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“…Baroreceptor denervation alone has been suggested to have little effect on the progression of heart failure, suggesting that baroreflexes are only a contributing factor to driving the increase in renal SNA (1). Other sympathoexcitatory reflex pathways such as those driven by the cardiac and carotid body chemoreceptors would appear to act in conjunction with any impairment in baroreflex function to drive the increases in renal SNA (7,17). A change in baroreflex function may not be essential for an increase in renal sympathetic drive in heart failure.…”

Section: R174 Ovarian Hormones Preserve Arterial Baroreflex Following MImentioning

confidence: 99%

Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats

Pinkham

Whalley

Guild

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Pinkham MI, Whalley GA, Guild SJ, Malpas SC, Barrett CJ. Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats. Am J Physiol Regul Integr Comp Physiol 309: R169-R178, 2015. First published May 20, 2015 doi:10.1152/ajpregu.00026.2015.-There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6 -7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P Ͻ 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 Ϯ 6 vs. 84 Ϯ 5% in male sham group) and OVX large MI group (37 Ϯ 3 vs. 75 Ϯ 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P Ͻ 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.

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Peripheral chemoreflex activation contributes to sympathetic baroreflex impairment in chronic heart failure

Cited by 74 publications

References 35 publications

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

Contribution of Autonomic Reflexes to the Hyperadrenergic State in Heart Failure

Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats

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