Abstract
Chronic heart failure (CHF) is a disease characterized by an overactive sympathetic nervous system. The kidney is especially vulnerable to these adaptations, and responds, in part, with a decrease in renal blood flow (RBF). The purpose of this study was to determine the effects of the α1 adrenergic receptor agonist phenylephrine (PE) and the nonselective adrenergic receptor agonist norepinephrine (NE) on RBF in sham and CHF animals. CHF was induced by coronary artery ligation. Anesthetized animals were instrumented with a renal flow probe and a catheter in the aorta close to the renal bifurcations. Changes in RBF were measured in response to intra‐aortic infusions of increasing doses of PE (5, 10, and 20 μg/kg) and NE (8 and 16 μg/kg). Renal cortices from CHF and sham animals were sieved to obtain a vascular‐enriched preparation. CHF animals exhibited a blunted change in RBF in response to intra‐aortic infusion of PE compared to sham animals at all concentrations. Conversely, CHF animals exhibited an increased sensitivity to NE. To determine if the changes in blood flow in response to ligand correlated to differential expression of the targeted receptors western blotting on sieved lysate was performed. Preliminary western blotting data indicate that relative amounts of β1 adrenergic receptor were significantly decreased in CHF animals compared to sham. Results of this study suggest that changes in RBF during CHF are due in part to alterations in adrenergic receptor signaling.
Published Version
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