Mechanisms of Sympathetic Activation in Heart Failure

Abstract

1. Heart Failure (HF) is a serious, debilitating condition with poor survival rates and an increasing level of prevalence. A characteristic of HF is a compensatory neurohumoral activation that increases with the severity of the condition. 2. The increase in sympathetic activity may be beneficial initially, providing inotropic support to the heart and peripheral vasoconstriction, but in the longer term it promotes disease progression and worsens prognosis. This is particularly true for the increase in cardiac sympathetic nerve activity, as shown by the strong inverse correlation between cardiac noradrenaline spillover and prognosis and by the beneficial effect of beta-adrenoceptor antagonists. 3. Possible causes for the raised level of sympathetic activity in HF include altered neural reflexes, such as those from baroreceptors and chemoreceptors, raised levels of hormones, such as angiotensin II, acting on circumventricular organs, and changes in central mechanisms that may amplify the responses to these inputs. 4. The control of sympathetic activity to different organs is regionally heterogeneous, as demonstrated by a lack of concordance in burst patterns, different responses to reflexes, opposite responses of cardiac and renal sympathetic nerves to central angiotensin and organ-specific increases in sympathetic activity in HF. These observations indicate that, in HF, it is essential to study the factors causing sympathetic activation in individual outflows, in particular those that powerfully, and perhaps preferentially, increase cardiac sympathetic nerve activity.

Transcatheter Aortic Valve Implantation Improves Cardiac Sympathetic Nerve Activity on ¹²³I-Metaiodobenzylguanidine Myocardial Scintigraphy in Severe Aortic Valve Stenosis

“…In fact, non-uniform sympathetic nerve responses have been reported. 41, 42 The plasma NE level, albeit a prognostic factor for HFrEF, 1 did not specifically reflect cardiac NE spillover. In fact, the plasma NE level did not correlate with AS severity.…”

“…Second is augmented sympathoexcitatory reflex, such as the arterial chemoreceptor and cardiac sympathetic afferent reflexes. 34 Central facilitation of the augmented cardiovascular sympathetic afferent reflex is mediated by increases in angiotensin-II and cytokines and a decrease in nitric oxide, which contribute to tonic enhancement of sympathetic output. 35,36 Figure 3.…”

Transient hypercapnic stress causes exaggerated and prolonged elevation of cardiac and renal interstitial norepinephrine levels in conscious hypertensive rats

“…Kamiya et al (11) reported that muscle SN activity parallels the renal and cardiac SN activity in response to baroreceptor pressure changes in anesthetized rabbits. In contrast, others have reported that central or peripheral stimuli cause selective and differential influences on the SN activity of each organ in anesthetized and conscious animals (13,36,37).Previous studies have shown that cardiovascular recovery from stress plays an important role in the pathogenesis of hypertension and is a predictor of overall mortality (1, 5). Sustained increases in SN activity after transient stress may accelerate cardiovascular damage.…”

“…Kamiya et al (11) reported that muscle SN activity parallels the renal and cardiac SN activity in response to baroreceptor pressure changes in anesthetized rabbits. In contrast, others have reported that central or peripheral stimuli cause selective and differential influences on the SN activity of each organ in anesthetized and conscious animals (13,36,37).…”

Influence of myocardial infarction on changes in the expression of angiotensin type 1 receptor in the rat prostate

“…A myocardial infarction initiates in the heart a sequence of humoral, neurogenic and hemodynamic events which influence the function of the heart and of remote organs. This progressive disorder must be man- www.fhc.viamedica.pl aged with regard to not only the state of the heart, but the condition of the circulation, lungs, neuroendocrine system and perhaps other organs like the prostate as well [7,8]. Several experimental and clinical studies have consistently shown that a myocardial infarction is associated with activation of the systemic RAS, and consequently increased concentration of angiotensin peptides in the blood and changes in angiotensin receptors (AT) expression [7,9].…”