title: Renal denervation in male rats with heart failure improves ventricular sympathetic nerve innervation and function.
abstract: Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for 4 wk before receiving bilateral RDx or sham RDx. After additional 3 wk, left ventricular (LV) function was assessed, and ventricular sympathetic nerve fiber density was determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue norepinephrine content (nerve fiber density in the LV of MI+sham RDx hearts was 0.31 ± 0.05% vs. 1.00 ± 0.10% in sham MI+sham RDx group,P< 0.05), and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14%,P< 0.05) and tissue norepinephrine content. MI was associated with an increase in fibrosis of the noninfarcted ventricular myocardium, which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared with pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart.
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Maximilian I
authors.initials: MI
authors.lastname: Pinkham
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Loftus
authors.affiliation: Department of Anatomy and Radiology, University of Auckland, Auckland, New Zealand.
authors.forename: Satya
authors.initials: S
authors.lastname: Amirapu
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Guild
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand; and.
authors.forename: Gina
authors.initials: G
authors.lastname: Quill
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon.
authors.forename: William R
authors.initials: WR
authors.lastname: Woodward
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Habecker
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand c.barrett@auckland.ac.nz.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Barrett
mesh_terms: D000818:Animals; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D006352:Heart Ventricles / Q000294:innervation* / Q000503:physiopathology; D007668:Kidney / Q000294:innervation* / Q000601:surgery; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D013562:Sympathectomy / Q000379:methods*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*
keywords: cardiac innervation; heart failure; renal nerve; sympathetic nerve activity