Angiotensin II and sympathetic activity in patients with congestive heart failure

Goldsmith, Steven R.; Hasking, Gregory J.; Miller, Elizabeth A.

doi:10.1016/0735-1097(93)90232-p

Cited by 32 publications

(18 citation statements)

References 22 publications

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“…A more confusing picture emerges in whole-animal experiments designed to isolate the contributions of the peripheral sympathetic nervous system: AII infusion can facilitate, 4 suppress, 5 or have no effect 6 on norepinephrine release from postganglionic sympathetic neurons. In humans, a similar pattern of sympathetic neural responses has been reported, with some studies showing increased norepinephrine spillover 3 and others showing no response 7 or decreased norepinephrine release 3,7,8 in response to AII. In other excitable cell types such as cardiomyocytes or vascular smooth muscle cells, a paradoxical response has also been reported.…”

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confidence: 75%

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

et al. 2003

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Abstract-Both stimulatory and suppressive responses of the sympathetic nervous system to angiotensin II (AII) Key Words: sympathetic nervous system Ⅲ angiotensin II Ⅲ calcium Ⅲ calcium channel blockers Ⅲ norepinephrine Ⅲ inositol T he renin-angiotensin and sympathetic nervous systems are homeostatically interconnected by a complex series of mutually reinforcing and mutually inhibiting interactions. In general, each of these systems tends to reinforce the pressor effects of the other as the two systems act to defend arterial pressure. Sympathetic stimulation is a major controller of juxtaglomerular cell renin release through the actions of catecholamines on juxtaglomerular cell ␤ 1 receptors. 1 The angiotensin II (AII) subsequently generated in the bloodstream can exert positive feedback on sympathetic nervous activity by several complex mechanisms, including direct stimulatory actions of AII on central and peripheral sympathetic neuronal activity and catecholamine release. [1][2][3] In addition to its stimulatory effects, AII can also suppress sympathetic neuronal activity in vivo. In animals and humans, complex reflex inhibition occurs when increases in arterial pressure stimulate arterial baroreflexes to cause reflex suppression of sympathetic nervous outflow. A more confusing picture emerges in whole-animal experiments designed to isolate the contributions of the peripheral sympathetic nervous system: AII infusion can facilitate, 4 suppress, 5 or have no effect 6 on norepinephrine release from postganglionic sympathetic neurons. In humans, a similar pattern of sympathetic neural responses has been reported, with some studies showing increased norepinephrine spillover 3 and others showing no response 7 or decreased norepinephrine release 3,7,8 in response to AII. In other excitable cell types such as cardiomyocytes or vascular smooth muscle cells, a paradoxical response has also been reported. AII treatment was shown to increase cytosolic calcium ([Ca 2ϩ ]i) by stimulation of IP 3 -dependent pathways 9,10 and was also reported to decrease [Ca 2ϩ ]i through enhanced calcium efflux. 11,12 The current studies were undertaken to examine the effects of AII on neuronal [Ca 2ϩ ]i and to investigate whether alterations in [Ca 2ϩ ]i play a role in the apparent "bidirectional" excitatory and suppressive responses to AII seen in sympathetic neurons studied in vivo. Using isolated primary sympathetic neurons from rats, we first related neuronal responses to the dose of AII and to the baseline [Ca 2ϩ ]i. To confirm that the same neuron is capable of both stimulatory and suppressive responses to AII, cells with spontaneously low [Ca 2ϩ ]i were exposed to a Ca 2ϩ ionophore and cells with spontaneously high [Ca 2ϩ ]i were exposed to nifedipine. We used losartan to investigate the role of the AT 1 receptors and confirmed IP 3 pathway dependency with an IP 3 receptor blocker and by prior

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confidence: 75%

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

et al. 2003

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“…Concerning relevance to heart failure, there are no studies in which angiotensin II has been introduced directly into the human central nervous system, but elegant work mainly by Zucker et al [20] has shown a role for central angiotensin II, acting through stimulation of nitric oxide, in the activation of the SNS in animal models of heart failure [20,22,23]. Presynaptic facilitation of norepinephrine release has been demonstrated in the normal human forearm circulation at very high concentrations of angiotensin II [24] but not in normal humans undergoing mild to moderate degrees of sympathostimulation during decreased central venous volume, nor has it been demonstrated in patients with heart failure with high baseline sympathetic tone [25][26][27][28]. However, a physiologic role for angiotensin II as an inhibitor of normal baroreflexmediated reduction in heart rate and sympathetic activity has been demonstrated in normal humans and animals [29,30].…”

Section: Effects Of the Raas On The Sympathetic Nervous Systemmentioning

confidence: 96%

“…The data come from studies that have examined the chronic effects of ACEI on sympathoactivation in heart failure. Acutely, administering ACEI therapy to a patient with heart failure does not have much, if any, effect on plasma norepinephrine or norepinephrine release [26]. However, after several months of therapy with ACEI, a reduction in muscle sympathetic nerve activity can be demonstrated, and in turn linked to an improvement in baroreflex function [32•].…”

Section: Effects Of the Raas On The Sympathetic Nervous Systemmentioning

confidence: 99%

Interactions between the sympathetic nervous system and the RAAS in heart failure

Goldsmith

2004

Curr Heart Fail Rep

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Therapy for heart failure caused by left ventricular systolic dysfunction is based on interference with maladaptive activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Agents that block beta-adrenergic receptors, decrease angiotensin-II formation, and antagonize the effects of angiotensin II and aldosterone have been shown to improve morbidity and mortality in this syndrome. Therefore, from a theoretical point of view, it would be desirable to actually diminish the degree of overactivity of these two homeostatic systems. There are compelling physiologic arguments and much experimental data to suggest that beta-adrenergic blockade may diminish activity of the RAAS. Conversely, angiotensin-converting enzyme inhibitors, angiotensin-II antagonists, and aldosterone antagonists may diminish activity of the SNS. Some clinical trials data may be interpreted in a fashion that suggests that part of the benefit of interfering with each system may relate to diminishing activity of the other. If true, combined therapy may lead to a virtuous cycle in which diminishing the adverse effects of each individual system is combined with reduced activity of the other. Such a cycle may be one factor underlying the impressive clinical results of recent neurohormonally based therapeutic trials and reinforces the need to look beyond acute hemodynamic effects of therapeutic agents when assessing their long-term impact in heart failure.

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“…There is also evidence, albeit conflicting, that the sympathetic nervous system is activated by the renin-angiotensin system. [1][2][3][4][5][6][7][8][9][10][11][12][13] This activation supposedly occurs through stimulation of angiotensin II receptors within the central nervous system and/or stimulation of presynaptic angiotensin II receptors located at sympathetic nerve terminals. When investigating the sympathetic nervous system and its interaction with the renin-angiotensin system, the heart is of particular interest.…”

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Exogenous Angiotensin II Does Not Facilitate Norepinephrine Release in the Heart

et al. 2002

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Abstract-Studies on the effect of angiotensin II on norepinephrine release from sympathetic nerve terminals through stimulation of presynaptic angiotensin II type 1 receptors are equivocal. Furthermore, evidence that angiotensin II activates the cardiac sympathetic nervous system in vivo is scarce or indirect. In the intact porcine heart, we investigated whether angiotensin II increases norepinephrine concentrations in the myocardial interstitial fluid (NE MIF ) under basal conditions and during sympathetic activation and whether it enhances exocytotic and nonexocytotic ischemia-induced norepinephrine release. In 27 anesthetized pigs, NE MIF was measured in the left ventricular myocardium using the microdialysis technique. Key Words: norepinephrine Ⅲ angiotensin II Ⅲ renin-angiotensin system Ⅲ sympathetic nervous system A ctivation of the sympathetic nervous system simultaneously leads to activation of the renin-angiotensin system via stimulation of ␤-adrenergic receptors within the kidney, resulting in an increased renin release. There is also evidence, albeit conflicting, that the sympathetic nervous system is activated by the renin-angiotensin system. 1-13 This activation supposedly occurs through stimulation of angiotensin II receptors within the central nervous system and/or stimulation of presynaptic angiotensin II receptors located at sympathetic nerve terminals. When investigating the sympathetic nervous system and its interaction with the renin-angiotensin system, the heart is of particular interest. First of all, the mammalian heart has a dense sympathetic innervation. Second, all components of the renin-angiotensin system are present in the heart, and most angiotensin II in the heart is formed from locally synthesized angiotensin I. 14 Third, in conditions like hypertension, ischemia, and especially heart failure, the renin-angiotensin system and sympathetic nervous system are both activated, and this activation likely contributes to the deterioration of cardiac function. [15][16][17] Evidence that angiotensin II activates the cardiac sympathetic nervous system in vivo is scarce 4 or indirect. 7,18 In a recent study, Teisman et al 4 have shown with the use of the microdialysis technique that "pharmacological" (10 Ϫ6 mol/L) concentrations of locally applied angiotensin II were associated with an increase in norepinephrine concentrations in the myocardial interstitial fluid (NE MIF ) of the in vivo rat heart. In the present study, we determined whether "physiological" (10 Ϫ10 mol/L) to "pathophysiological" (10 Ϫ8 mol/L) concentrations of angiotensin II modulate NE MIF in the intact porcine heart. The pig is especially suitable as a model for studying the cardiac sympathetic nervous system because, unlike the rat, the prevailing parasympathetic control of cardiac function is very similar to that in man, which allows for a more reliable extrapolation of the experimental results to the reality of human patients.To exclude a masking effect of neuronal norepinephrine reuptake and negative feedback through pr...

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Angiotensin II and sympathetic activity in patients with congestive heart failure

Cited by 32 publications

References 22 publications

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Interactions between the sympathetic nervous system and the RAAS in heart failure

Exogenous Angiotensin II Does Not Facilitate Norepinephrine Release in the Heart

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