Alpha-adrenergic mechanisms in the pathophysiology of left ventricular heart failure--an analysis of their role in systolic and diastolic dysfunction.
Alpha-adrenoceptor (alpha-AR) mechanisms may contribute to systolic and diastolic dysfunction of the left ventricle. Centrally acting alpha 2-AR agonist drugs, including methyldopa, clonidine, and guanabenz, activate brainstem alpha 2-AR and this activation results in a decrease in overall sympathetic tone and an increase in parasympathetic tone. Peripherally acting alpha 1-AR antagonists, such as prazosin, inhibit the actions of catecholamines at post-synaptic receptor sites. Heart failure is characterized by hyperactivity of sympathetic pathways and parasympathetic withdrawal. In this situation, alpha 2-agonists reduce sympathetic activity and improve hemodynamic parameters of cardiac function; both acute and chronic administration of alpha 2-AR have been demonstrated to reduce serum catecholamine levels, heart rate, and arterial blood pressure, and to improve exercise performance. Diastolic dysfunction of the left ventricle is characterized by a marked decrease in ventricular compliance, often a result of hypertension and left ventricular hypertrophy; the end result is an increase in left ventricular filling pressure and pulmonary venous pressure. Treatment with alpha 2-AR, by decreasing sympathetic tone and blood pressure, and alpha 1-AR antagonists, by reducing blood pressure and by directly inhibiting the actions of catecholamines at alpha 1-AR, may produce a reduction in the degree of ventricular hypertrophy and improve diastolic performance of the left ventricle. Thus, therapeutic intervention in heart failure with either alpha 2-AR agonists or alpha 1-AR antagonists may favorably modulate these alterations in sympathetic tone and improve ventricular function.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D001341:Autonomic Nervous System / Q000187:drug effects / Q000648:ultrastructure; D002490:Central Nervous System / Q000187:drug effects / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D003000:Clonidine / Q000494:pharmacology; D003971:Diastole / Q000187:drug effects; D006143:Guanabenz / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology / Q000648:ultrastructure; D006801:Humans; D008750:Methyldopa / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013318:Stroke Volume; D013599:Systole / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D008750:Methyldopa; D006143:Guanabenz; D003000:Clonidine