Mechanisms of sympatho-inhibition following renal and cardiac denervation in heart failure

In experimental chronic heart failure (CHF), sympatho-excitatory reflexes are initiated by enhanced input from sensory endings in e.g. carotid bodies, cardiac sympathetic afferents and renal afferents. Experiments carried out a rapid pacing model of CHF in the rabbit support the notion that renal denervation lowers sympathetic outflow and enhances arterial baroreflex function. Renal denervation also improved cardiac sympatho-vagal balance and reduced heart rate variability. Renal denervation in rabbits with pacing-induced CHF also leads to increased renal blood flow. Importantly renal denervation reduced the exaggerated renal vasoconstriction in response to acute exercise and hypoxia in rabbits with CHF. Finally, Angiotensin II receptor expression and oxidative stress was decreased in the denervated renal cortex of rabbits with CHF. The heart is innervated by afferent endings that traverse sympathetic pathways and, in part, transmit sensation of pain during ischemia. Selective cardiac sympathetic afferent ablation using resiniferatoxin (RTX) applied to the surface of the heart at the time of coronary ligation also led to reduced sympathetic outflow, increased baroreflex gain, less cardiac fibrosis and greater cardiac compliance several weeks post myocardial infarction. These studies strongly suggest that both afferent and efferent pathways participate in the benefits of renal denervation in the CHF state. These experiments point to an important role for chronic denervation in the modulation of autonomic outflow in CHF. As is the case for drug-resistant hypertension, renal denervation may be an effective therapy for CHF.