title: Physiology and pharmacology of the cardiovascular adrenergic system.
abstract: Heart failure (HF), the leading cause of death in the western world, ensues in response to cardiac injury or insult and represents the inability of the heart to adequately pump blood and maintain tissue perfusion. It is characterized by complex interactions of several neurohormonal mechanisms that get activated in the syndrome in order to try and sustain cardiac output in the face of decompensating function. The most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are greatly elevated in HF. Acutely, provided that the heart still works properly, this activation of the ANS will promptly restore cardiac function according to the fundamental Frank-Starling law of cardiac function. However, if the cardiac insult persists over time, this law no longer applies and ANS will not be able to sustain cardiac function. This is called decompensated HF, and the hyperactive ANS will continue to "push" the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, and, finally, the molecular alterations in heart physiology that occur in HF along with their pharmacological and therapeutic implications for the failing heart.
authors.affiliation: Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy Fort Lauderdale, FL, USA.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Lymperopoulos
keywords: adrenal gland; adrenergic nervous system; adrenergic receptor; cardiac myocyte; catecholamine; heart failure
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