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First published online on March 20, 2008.
Experimental Physiology (2008)
DOI: 10.1113/expphysiol.2007.040261
© The Physiological Society 2008

A more recent version of this article appeared on May 1, 2008
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Received January 11, 2008
Revised February 7, 2008
Accepted after revision March 13, 2008


Autonomic Neuroscience [200]

Solitary Tract Nucleus ACE2 Inhibitor MLN4760 Injections Reduce Baroreceptor Reflex Sensitivity for Heart Rate Control

Debra I Diz 1*, Maria A Garcia-Espinosa 1, Stephen Gegick 1, Ellen N Tommasi 1, Carlos M Ferrario 1, E. Ann Tallant 1, Mark C Chappell 2, Patricia E Gallagher 1

1 Wake Forest University School of Medicine
2 Wake Forest University

* To whom correspondence should be addressed. E-mail: ddiz{at}wfubmc.edu.


   Abstract
Injections of the 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 AT1 antagonist candesartan increase BRS by 40% when reflex bradycardia is assessed. The enzyme angiotensin converting enzyme 2 (ACE2) is known to convert angiotensin (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 (SD) rats. Moreover, we show that BRS for reflex bradycardia is attenuated (1.16 +/- 0.29 msec/mm Hg before versus 0.33 +/- 0.11 msec/mm Hg; p < 0.05; n = 8) 30 - 60 minutes following injection of the selective ACE2 inhibitor, MLN4760 (12 pmol/120 nL), into the nucleus of the solitary tract (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 to increases in arterial pressure.

Key Words: Angiotensin, Arterial baroreflex, Enzyme




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