Abstract

Renal nerve denervation (DNx) is currently being assessed as a therapy for drug-resistant hypertension and other disorders characterized by sympatho-excitation, such as chronic heart failure (CHF). We hypothesized that renal DNx enhances arterial baroreflex (BR) control of heart rate (HR) in normal and CHF rabbits. All animals were instrumented with ventricular pacing leads and an arterial pressure (AP) radiotelemetry transducer. After recovery the left kidney was denervated by stripping the renal artery of all visible fibers. Intact animals were subjected to a sham operation. Two weeks later, CHF animals were subjected to rapid ventricular pacing. BR changes in HR and AP were induced by iv sodium nitroprusside and phenylephrine (PE) infusions alone and after injection of atropine or metoprolol. BR function was determined by fitting mean AP and HR data to a 4 parameter logistic equation. Renal DNx increased HR range from 156 ± 34 bpm in intact rabbits compared to 298 ± 39 bpm in DNx rabbits (p = 0.022). This was primarily due to a decrease in the minimum HR following PE infusion. During blockage with metoprolol HR range was increased from 140 ± 39.35 bpm in Sham to 262.75 ± 9.97 bpm in DNx rabbits (p = 0.016) suggesting an improvement in the vagal components of BR function. In intact rabbits with CHF, HR range was 110 ± 16 bpm compared to 294 ± 15 bpm in CHF renal DNx animals (p = .002). These data suggest renal DNx enhances the autonomic components of BR control of HR in the normal and CHF states.

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