ANGIOTENSIN‐(1‐7) ICV CHRONIC INFUSION IMPROVES BAROREFLEX CONTROL OF RENAL SYMPATHETIC NERVE ACTIVITY IN DOCA‐SALT HYPERTENSIVE RATS

Abstract

We evaluated the effect of angiotensin‐(1‐7) [Ang‐(1‐7)] ICV chronic infusion in baseline and baroreflex control of renal sympathetic nerve activity (RSNA) in DOCA‐salt hypertensive rats. Sprague‐Dawley rats were submitted to uninephrectomy (UNX) or DOCA‐salt hypertension model (UNX + DOCA + saline). After 7 days, Ang‐(1‐7) ICV infusion (0.2 nmol/ 0.5 μl/ hour) or 0.9% sterile saline (0.5 μl/ hour) was initiated by osmotic mini‐pumps for 14 days. On the 21th day, the animals were anaesthetized (urethane; i.p.) and baseline arterial pressure (MAP), heart rate (HR) and RSNA, and baroreflex control RSNA were evaluated. As expected, DOCA‐salt treatment induced an increase in baseline MAP (122 ± 3 mmHg, n=4 vs 93 ± 2 mmHg, n=5, UNX), reduced baroreflex control of RSNA (1.33 ± 0.10 %ΔRSNA/ mmHg, n=4 vs 2.73 ± 0.29 %ΔRSNA/ mmHg, n=5, UNX), without any changes in baseline HR or RSNA (130 ± 17 spikes/sec, n=5 vs 118 ± 12 spikes/sec, n=4 UNX). Animals submitted to Ang‐(1‐7) ICV infusion presented a reduced MAP (conscious rats) and a greater baroreflex control of RSNA (2.24 ± 0.20 %ΔRSNA/ mmHg, n=4), without any significant in baseline RSNA (113 ± 10 spikes/sec, n=4). These results showed that central Ang‐(1‐7) modulates baroreflex control of RSNA in DOCA‐salt rats, and suggest that chronic increase in Ang‐(1‐7) levels in the brain may attenuate high blood pressure, in part by improving baroreflex control of sympathetic activity.