title: Central angiotensin (1-7) enhances baroreflex gain in conscious rabbits with heart failure.
abstract: In chronic heart failure (CHF), arterial baroreflex function is impaired, in part, by activation of the central renin-angiotensin system. A metabolite of angiotensin (Ang) II, Ang-(1-7), has been shown to exhibit cardiovascular effects that are in opposition to that of Ang II. However, the action of Ang-(1-7) on sympathetic outflow and baroreflex function is not well understood, especially in CHF. The aim of this study was to determine the effect of intracerebroventricular infusion of Ang-(1-7) on baroreflex control of heart rate and renal sympathetic nerve activity in conscious rabbits with CHF. We hypothesized that central Ang-(1-7) would improve baroreflex function in CHF. Ang-(1-7) (2 nmol/1 μL per hour) or artificial cerebrospinal fluid (1 μL per hour) was infused by an osmotic minipump for 4 days in sham and pacing-induced CHF rabbits (n=3 to 6 per group). Ang-(1-7) treatment had no effects in sham rabbits but reduced heart rate and increased baroreflex gain (7.4±1.5 versus 2.5±0.4 bpm/mm Hg; P<0.05) in CHF rabbits. The Ang-(1-7) antagonist A779 (8 nmol/1 μL per hour) blocked the improvement in baroreflex gain in CHF. Baroreflex gain increased in CHF+Ang-(1-7) animals when only the vagus was allowed to modulate baroreflex control by acute treatment with the β-1 antagonist metoprolol, indicating increased vagal tone. Baseline renal sympathetic nerve activity was significantly lower, and baroreflex control of renal sympathetic nerve activity was enhanced in CHF rabbits receiving Ang-(1-7). These data suggest that augmentation of central Ang-(1-7) inhibits sympathetic outflow and increases vagal outflow in CHF, thus contributing to enhanced baroreflex gain in this disease state.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Kar
authors.forename: Lie
authors.initials: L
authors.lastname: Gao
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Belatti
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Curry
authors.forename: Irving H
authors.initials: IH
authors.lastname: Zucker
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology*; D002908:Chronic Disease; D003243:Consciousness / Q000502:physiology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D057967:Infusions, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D008790:Metoprolol; C118790:angiotensin I (1-7)