All Volumes (2001-2008)

Volume

Volume II, 2002

Document Type

Article

Publication Date

2002

Abstract

Heart failure is the inability of body's cardiac output to keep pace with its demand for supplies and waste removal. It is characterized by systolic and diastolic ventricular dysfunction, cardiac remodeling, myocyte loss and fibrosis (Nyquist-Battie et al, 1996). It is accompanied by an increase in sympathetic activity with measurable increases in circulating plasma norepinephrine levels (Hasegawa et al. 2001; Kaye et al., 1995). Previous studies have suggested that adrenergic agonists play a role in myocardial cell death. Mann et al. (1992) have shown that increased activation of the adrenergic signaling pathway causes necrotic as well as apoptotic death in cardiomyocytes. It is the goal of this study to determine by which adrenergic receptor-dependent pathway cell death is induced α1, β1, or β2. After determining which pathway(s) are involved, this study will attempt to clarify by which mechanism myocyte death occurs-necrosis or apoptosis. It is our hope that the data we provide might have some value for future therapeutic treatments of heart failure. Three types of adrenergic receptors are found on cardiomyocytes: α1, β1, and β2. To examine each pathway, three adrenergic agonists were chosen: norepinephrine, isoproterenol, and phenylephrine. Norepinephrine was chosen because it stimulates α1 and β1 adrenergic receptors, with a high affinity for β1. Isoproterenol was chosen because it stimulates β1 and β2 adrenergic receptors, with a high affinity for β2. Phenylephrine was chosen because of its stimulatory nature on α1 receptors.

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