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Hypertension & Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Injections of the angiotensin(1–7) [Ang(1–7)] antagonist [D-Ala7]-Ang(1–7) into the nucleus of the solitary tract (NTS) of Sprague–Dawley rats reduce baroreceptor reflex sensitivity (BRS) for control of heart rate by
40%, whereas injections of the angiotensin II (Ang II) type 1 receptor antagonist candesartan increase BRS by 40% when reflex bradycardia is assessed. The enzyme angiotensin-converting enzyme 2 (ACE2) is known to convert Ang II to Ang(1–7). We report that ACE2 activity, as well as ACE and neprilysin activities, are present in plasma membrane fractions of the dorsomedial medulla of Sprague–Dawley rats. Moreover, we show that BRS for reflex bradycardia is attenuated (1.16 ± 0.29 ms mmHg–1 before versus 0.33 ± 0.11 ms mmHg–1 after; P < 0.05; n
= 8) 30–60 min following injection of the selective ACE2 inhibitor MLN4760 (12 pmol in 120 nl) into the NTS. These findings support the concept that within the NTS, local synthesis of Ang(1–7) from Ang II is required for normal sensitivity for the baroreflex control of heart rate in response to increases in arterial pressure.
(Received 11 January 2008;
accepted after revision 13 March 2008; first published online 20 March 2008)
Corresponding author D. I. Diz: The Hypertension & Vascular Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032, USA. Email: ddiz{at}wfubmc.edu
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