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Experimental Physiology 93.5 pp 694-700
DOI: 10.1113/expphysiol.2007.040261
© The Physiological Society 2008
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Injections of angiotensin-converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats

Debra I. Diz1, Maria A. Garcia-Espinosa1, Stephen Gegick1, Ellen N. Tommasi1, Carlos M. Ferrario1, E. Ann Tallant1, Mark C. Chappell1 and Patricia E. Gallagher1

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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M. K. Raizada and J. F. R. Paton
Recent advances in the renin-angiotensin system: angiotensin-converting enzyme 2 and (pro)renin receptor
Exp Physiol, May 1, 2008; 93(5): 517 - 518.
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