Neurohumoral Activation in Heart Failure

Abstract

In patients with heart failure (HF), the neuroendocrine systems of the sympathetic nervous system (SNS), the renin–angiotensin–aldosterone system (RAAS) and the arginine vasopressin (AVP) system, are activated to various degrees producing often-observed tachycardia and concomitant increased systemic vascular resistance. Furthermore, sustained neurohormonal activation plays a key role in the progression of HF and may be responsible for the pathogenetic mechanisms leading to the perpetuation of the pathophysiology and worsening of the HF signs and symptoms. There are biomarkers of activation of these neurohormonal pathways, such as the natriuretic peptides, catecholamine levels and neprilysin and various newer ones, which may be employed to better understand the mechanisms of HF drugs and also aid in defining the subgroups of patients who might benefit from specific therapies, irrespective of the degree of left ventricular dysfunction. These therapies are directed against these neurohumoral systems (neurohumoral antagonists) and classically comprise beta blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers and vaptans. Recently, the RAAS blockade has been refined by the introduction of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan, which combines the RAAS inhibition and neprilysin blocking, enhancing the actions of natriuretic peptides. All these issues relating to the neurohumoral activation in HF are herein reviewed, and the underlying mechanisms are pictorially illustrated.

The protective role of ginsenoside Rg3 in heart diseases and mental disorders

“…Persistent catecholamine elevation may cause myocardial calcium overload in cytosolic and mitochondrial compartments, trigger oxidative stress, increase mitochondrial permeability, and cell death ( Szatko et al, 2023 ). In patients with HF, there is an activation of the neuroendocrine systems, particularly the sympathetic nervous system and the renin-angiotensin-aldosterone system, leading to elevated levels of neurohormones such as catecholamines ( Manolis et al, 2023 ). Dopamine, an important catecholamine, plays a crucial role in regulating various mental and physical functions, including anxiety, fear, attention deficit hyperactivity disorder (ADHD), and schizophrenia ( Jayanti et al, 2023 ).…”

Heart Rate Recovery: Up to Date in Heart Failure—A Literature Review

“…Heart failure, which will be thoroughly discussed further, has intricate connections with dysautonomia, implicit with the consequences of hypersympathetic states. Autonomic nervous system dysfunction is also implied in conditions such as hypertension [ 3 ], diabetes mellitus (DM) [ 37 ], metabolic syndrome and obesity [ 38 ], and obstructive sleep apnea syndrome [ 39 ].…”

“…It is typically measured as the difference between the maximum heart rate during effort and the heart rate at a given recovery time [ 1 , 2 ]. It serves as a precious tool for evaluating autonomic nervous system (ANS) imbalance and has been widely used in screening and quantifying cardiovascular risk and all-cause mortality in patients suffering from heart disease [ 3 , 4 ]. This process reflects the dynamic equilibrium and synchronized interaction between the reactivation of the parasympathetic nervous system and the withdrawal of the sympathetic nervous system [ 5 ].…”

Editorial for the IJMS Special Issue on Sglt2 Inhibitors (Volume 2)

“…Finally, the effects of empagliflozin in cardiac sympathetic activation and inflammatory cell infiltration due to angiotensin II (AngII)-dependent hypertension were tested by Castoldi et al [9]. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory cell infiltration, and tyrosine hydroxylase (the rate-limiting enzyme in catecholamine biosynthesis [10]) upregulation induced by Ang II treatment in Sprague-Dawley rats, indicating reverse-remodeling, anti-inflammatory, and sympatholytic effects for this SGLT2i [9]. Interestingly, empagliflozin did not affect blood glucose or Ang II-induced increase in blood pressure in these animals.…”