The overall goal of this project is further understanding of the mechanisms underlying the exaggerated reflex renal vasoconstriction in humans with heart failure during exercise. The hallmark of congestive heart failure is decreased exercise tolerance, often accompanied by volume overload. Although the mechanisms underlying this exercise intolerance are multifactorial, abnormal reflex control of the renal circulation is likely an important component. In preliminary studies the investigators have observed an exaggerated reflex renal vasoconstriction during exercise in humans with heart failure. Both the magnitude and the duration of the reflex renal vasoconstriction are augmented in heart failure patients compared with controls. An exaggerated increase in renal vasoconstriction could potentially contribute to the decrease in exercise capacity by increasing afterload, which in heart failure patients would blunt the expected exercise-induced increase in cardiac output. The goal of the study is to determine the underlying afferent and efferent reflex mechanisms modulating renal vascular resistance in humans with heart failure and compare these mechanisms to those of normal humans. NYHA functional class III-IV heart failure patients and age and gender matched normal volunteers will be studied. Renal blood flow will be measured using dynamic PET with the blood flow agent O-15 water. The following mechanisms, which alone or in combination, are likely to contribute to the exaggerated renal vasoconstriction during exercise in patients with heart failure will be tested: l) attenuated arterial baroreflex buffering of renal vasoconstriction will be tested by the neck collar device; 2) sensitization of muscle mechanoreceptors will be tested by dynamic exercise and involuntary muscle contraction; 3) augmented influence of central command will be tested at the onset of low intensity exercise, and following local nerve block (Bier block); 4) sensitization of the renin-angiotensin system will be tested using pharmacological blockade. Improved understanding of reflex control of the renal circulation during exercise in advanced heart failure patients is critical to developing better therapies to decrease morbidity and mortality in patients with congestive heart failure.
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