Central Ang‐(1–7) reduces sympathetic nerve activity in conscious rabbits with heart failure

In chronic heart failure (CHF), impairment of arterial baroreflex function and elevated sympathetic nerve activity are due in part to activation of the central renin‐angiotensin system. A metabolite of Angiotensin II (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 nerve activity and baroreflex function is poorly understood, especially in CHF. We tested the hypothesis that intracerebroventricular (ICV) infusion of Ang‐(1–7) would reduce resting renal sympathetic nerve activity (RSNA) and improve baroreflex control of RSNA in rabbits with CHF. Ang‐(1–7) (2 nmol/μl/hour) or artificial cerebrospinal fluid (1 μl/hour) was infused ICV by an osmotic mini‐pump for 3–5 days in sham and pacing‐induced CHF rabbits (n=3–4/group). CHF rabbits showed increased resting RSNA and depressed baroreflex gain in the conscious state. Ang‐(1–7) treatment in CHF reduced resting RSNA (CHF+Ang‐(1–7): 22.2±2.0% of max vs. CHF+aCSF: 57.9±12.5% of max, P<.05) and increased baroreflex gain (CHF+Ang‐(1–7): 6.8±1.0 % of max/mm Hg vs. CHF+aCSF: 3.1±0.1 % of max/mm Hg, P<.05). These data suggest that augmentation of central Ang (1–7) inhibits sympathetic outflow in the CHF state and are consistent with the view that Ang (1–7) action opposes that of Ang II in the central nervous system. Source of support: PO1 HL‐62222