The origin of sympathetic outflow in heart failure: the roles of angiotensin II and nitric oxide

Zucker, Irving H.; Schultz, Harold D.; Li, Yi Fan; Wang, Yu; Wang, Wei; Patel, Kaushik P.

doi:10.1016/j.pbiomolbio.2003.11.010

Cited by 170 publications

(185 citation statements)

References 131 publications

(58 reference statements)

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“…It is well documented that either NOS activity or NO production is decreased in various tissues in the CHF state (Zucker et al 2004). These data imply that a possible reduction of NO release in the CB in the CHF state would lead to a disinhibition of CB chemoreceptors and elevate activity during normoxia, and even contribute to the enhanced afferent sensitivity to hypoxia.…”

Section: Role Of No On Cb Function In Chfmentioning

confidence: 85%

“…The impaired baroreflex sensitivity (Zucker et al 2004) and enhanced CB chemoreflex sensitivity, both characteristic of patients and experimental animals with CHF, are likely then to act synergistically to enhance sympathetic activity. There is a close correlation between enhanced peripheral chemoreflex sensitivity and impaired baroreflex sensitivity in CHF patients (Ponikowski & Banasiak, 2001).…”

Section: Central Interaction With Other Reflexes and Brainstem Mechanmentioning

confidence: 99%

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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: 85%

Section: Central Interaction With Other Reflexes and Brainstem Mechanmentioning

confidence: 99%

Carotid body function in heart failure

Schultz

2007

Respiratory Physiology & Neurobiology

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“…These adaptations may occur via neural remodeling or endogenous factors, such as nitric oxide. 20,[42][43][44][45][46] These adaptations would promote a decrease in sympathetic autonomic influence and an increase in the participation of the vagal autonomic component in cardiac control to improve the autonomic balance. Additionally, physical exercise may also exacerbate the influence of angiotensin II on the modulation activity in specific neural sites, 45 but further investigation is required.…”

Section: Discussionmentioning

confidence: 99%

Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment

et al. 2011

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We investigated the influence of angiotensin-converting enzyme inhibitor (ACEi) treatment and physical exercise on arterial pressure (AP) and heart rate variability (HRV) in volunteer patients with hypertension. A total of 54 sedentary volunteers were divided into three groups: normotensive (NT Group), hypertensive (HT Group) and HT volunteers treated with ACEi (ACEi Group). All volunteers underwent an aerobic physical-training protocol for 15 weeks. HRV was investigated using a spectral analysis of a time series of R-R interval (RRi) that was obtained in a supine position and during a tilt test. Physical training promoted a significant reduction in the mean arterial pressure of the HT group (113 ± 3 vs. 106 ± 1 mm Hg) and the ACEi group (104 ± 2 vs. Keywords: aerobic physical training; angiotensin; heart rate variability INTRODUCTION Hypertension is highly prevalent in the adult population and represents one of the leading causes of morbidity and mortality worldwide. 1,2 This condition is directly related to the development of cardiovascular diseases, encephalic vascular accident and renal insufficiency. 3 The risk factors for hypertension are associated with many other factors, including lifestyle. 4 The excessive ingestion of salt and alcohol, obesity, smoking and sedentariness represent the main behavioral factors that contribute to the occurrence and development of hypertension. 5 The treatment of hypertension consists mainly of a pharmacological approach, and the angiotensin-converting enzyme inhibitors (ACEis) are an important class of medications. 6 ACEis reduce arterial pressure (AP) by decreasing the peripheral vascular resistance, and they reduce cardiac hypertrophy and the proliferation of vascular smooth muscle cells. 7-9 Additionally, ACEis have an important role in cardiac autonomic control. Some studies have shown that ACEi treatment of hypertension in experimental animals and humans improves baroreflex

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“…Three possible mechanisms for this observation can be suggested. First, nitric oxide (NO) is known to possess central sympathoinhibitory effects and sildenafil, by potentiating the biologic effects of NO, could reduce central sympathetic outflow [16,17]. Second, the prejunctional effects of NO on norepinephrine release could explain the cardiac sympathoinhibitory effect of sildenafil [18].…”

Section: Discussionmentioning

confidence: 99%

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Al‐Hesayen

Floras

Parker

2006

European J of Heart Fail

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Background: Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase-5 inhibition on sympathetic activity in this population has not been evaluated. Methods and results: 10 patients with heart failure (ejection fraction 23 T 3%) were studied. Generalized and cardiac sympathetic activity responses to an intravenous infusion of sildenafil were measured by the norepinephrine spillover method. In response to sildenafil, there was a significant reduction in mean pulmonary artery (À 26 T 5%, P < 0.01) and mean arterial pressures (À 8 T 1%, P < 0.01). These hemodynamic responses were accompanied by a 22 T 5% reduction in cardiac norepinephrine spillover ( P < 0.02) but no change in total body norepinephrine spillover. Conclusions: The acute administration of sildenafil is associated with a modest reduction in systemic arterial blood pressure and a more substantial reduction in pulmonary arterial pressure. These hemodynamic changes are observed in the absence of systemic sympathetic activation and are associated with a reduction in cardiac norepinephrine spillover in patients with chronic heart failure. These observations are relevant given the high prevalence of erectile dysfunction in this patient population.

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The origin of sympathetic outflow in heart failure: the roles of angiotensin II and nitric oxide

Cited by 170 publications

References 131 publications

Carotid body function in heart failure

Carotid body function in heart failure

Physical exercise improves cardiac autonomic modulation in hypertensive patients independently of angiotensin-converting enzyme inhibitor treatment

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

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