title: Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with β-receptor blockade.
abstract: Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and β1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of β-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Heitaro
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyaji
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D013562:Sympathectomy; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D014446:Tyrosine 3-Monooxygenase; D017298:Bisoprolol