Being Adrenergic
Heart failure is a clinical syndrome that occurs over time after a cardiac injury or chronic stress causing a decline in contractile function of this pumping efficiency of the heart. It is marked by a dynamic interplay between underlying myocyte dysfunction and compensatory mechanisms that are neurohumoral in nature as these signals attempt to stimulate the pump to maintain cardiac output. Among these neurohormonal mechanisms, elevated activities of the adrenergic nervous system, of the renin–angiotensin–aldosterone system, and of several cytokines play central roles.These systems are initially activated to compensate for the reduced cardiac function and to maintain cardiac output. However, upon long-term presence of the initial insult to the heart muscle, cardiac function ultimately succumbs to their deleterious effects on myocytes and other cells of the heart, leading to cardiac decompensation and progressively worsening function and the inability to sustain daily life activities. The present review discusses the role of the ANS in HF pathophysiology and therapeutics, starting with a discussion of its role in normal cardiac function.
The human heart also expresses at much lower levels than of total. How important a role cardiac play in cardiac physiology is still a matter of debate. In contrast, their role in regulation of blood flow by inducing constriction in the smooth muscle wall of major arteries is well-known and indisputable. The end result is again raised intracellular, which leads to contraction.
A vast number of studies over the past few decades have established the crucial role of activated ANS in the compensatory response of the circulation to retain its hemodynamic stability in the face of a cardiac insult and, when this fails, its excessive activation that accelerates HF progression and poses severe toxicity on the chronically failing heart. Additionally, the benefits of blockers and other therapeutic modalities that mitigate or protect the heart against this ANS hyperactivity are also well-documented. Several recent developments in the basic cardiovascular research field that are at various stages of preclinical testing to ultimately reach the bedside in HF therapeutics also aim at reducing the activity and the detrimental effects of the ANS on the failing heart. Among these are sympatholytic agents, polymorphic variants of cardiac ARs that confer better prognosis in HF or better responses to current HF treatments, new sympathomimetics that seek to augment the function of the seemingly cardioprotective while simultaneously blocking the cardiotoxic, activation of the cardiac parasympathetic nervous system, and, last but not least, augmentation of cardiac dependent function without the accompanying elevation of ANS activity/outflow. The latter is pursued with the promising inhibition therapeutic approach, which poses to improve cardiac adrenergic and inotropic reserves by restoring cardiac signaling and function while keeping the ANS outflow at bay by restoring or augmenting central, cardiac, and adrenal sympathoinhibitory function. Further understanding of the mechanisms of ANS activation and of the repercussions this has on regulation of cardiac function and structure in chronic HF is most certainly bound to provide the clinicians of the future with some desperately needed, newer, and better weapons in the battle against this devastating disease.
The human heart also expresses at much lower levels than of total. How important a role cardiac play in cardiac physiology is still a matter of debate. In contrast, their role in regulation of blood flow by inducing constriction in the smooth muscle wall of major arteries is well-known and indisputable. The end result is again raised intracellular, which leads to contraction.
A vast number of studies over the past few decades have established the crucial role of activated ANS in the compensatory response of the circulation to retain its hemodynamic stability in the face of a cardiac insult and, when this fails, its excessive activation that accelerates HF progression and poses severe toxicity on the chronically failing heart. Additionally, the benefits of blockers and other therapeutic modalities that mitigate or protect the heart against this ANS hyperactivity are also well-documented. Several recent developments in the basic cardiovascular research field that are at various stages of preclinical testing to ultimately reach the bedside in HF therapeutics also aim at reducing the activity and the detrimental effects of the ANS on the failing heart. Among these are sympatholytic agents, polymorphic variants of cardiac ARs that confer better prognosis in HF or better responses to current HF treatments, new sympathomimetics that seek to augment the function of the seemingly cardioprotective while simultaneously blocking the cardiotoxic, activation of the cardiac parasympathetic nervous system, and, last but not least, augmentation of cardiac dependent function without the accompanying elevation of ANS activity/outflow. The latter is pursued with the promising inhibition therapeutic approach, which poses to improve cardiac adrenergic and inotropic reserves by restoring cardiac signaling and function while keeping the ANS outflow at bay by restoring or augmenting central, cardiac, and adrenal sympathoinhibitory function. Further understanding of the mechanisms of ANS activation and of the repercussions this has on regulation of cardiac function and structure in chronic HF is most certainly bound to provide the clinicians of the future with some desperately needed, newer, and better weapons in the battle against this devastating disease.
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