title: ACE inhibition improves cardiac NE uptake and attenuates sympathetic nerve terminal abnormalities in heart failure.
abstract: Cardiac sympathetic nerve terminal dysfunction plays an important role in the downregulation of myocardial beta-adrenoceptors in heart failure. To determine whether chronic angiotensin-converting enzyme (ACE) inhibition improved cardiac sympathetic nerve terminal function and hence increased myocardial beta-adrenergic responsiveness, we administered ACE inhibitors to dogs with chronic right-sided heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. The RHF animals exhibited fluid retention, elevated right heart filling pressures, blunted inotropic response to isoproterenol, and reduced beta-adrenoceptor density. These changes were accompanied by decreases in right ventricular norepinephrine (NE) uptake and neuronal NE histofluorescence and tyrosine hydroxylase immunoreactive profiles. ACE inhibitors had no effect on the production of heart failure but greatly reduced the attenuation of cardiac NE uptake, neuronal NE histofluorescence, and tyrosine hydroxylase immunoreactive profiles. ACE inhibition also improved the inotropic response to isoproterenol and restored myocardial beta-adrenoceptor density. The changes probably are caused by reduction of cardiac NE release by ACE inhibition and may contribute to the beneficial effects of ACE inhibitor therapy in patients with chronic heart failure.
authors.affiliation: Cardiology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: T H
authors.initials: TH
authors.lastname: Fan
authors.forename: E
authors.initials: E
authors.lastname: Dong
authors.forename: R A
authors.initials: RA
authors.lastname: Siddiqui
authors.forename: A
authors.initials: A
authors.lastname: Yatani
authors.forename: S Y
authors.initials: SY
authors.lastname: Stevens
authors.forename: C S
authors.initials: CS
authors.lastname: Liang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D005453:Fluorescence; D006038:Glyoxylates / Q000494:pharmacology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics; D009206:Myocardium / Q000378:metabolism*; D009411:Nerve Endings / Q000201:enzymology / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000201:enzymology / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D006038:Glyoxylates; D011943:Receptors, Adrenergic, beta; D004656:Enalapril; D014446:Tyrosine 3-Monooxygenase; D007703:Peptidyl-Dipeptidase A; C031150:glyoxylic acid; D017257:Ramipril; D009638:Norepinephrine