Premium
Injections of angiotensin‐converting enzyme 2 inhibitor MLN4760 into nucleus tractus solitarii reduce baroreceptor reflex sensitivity for heart rate control in rats
Author(s) -
Diz Debra I.,
GarciaEspinosa Maria A.,
Gegick Stephen,
Tommasi Ellen N.,
Ferrario Carlos M.,
Ann Tallant E.,
Chappell Mark C.,
Gallagher Patricia E.
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2007.040261
Subject(s) - baroreflex , baroreceptor , medicine , reflex bradycardia , endocrinology , solitary nucleus , angiotensin ii , reflex , bradycardia , candesartan , angiotensin ii receptor type 1 , heart rate , chemistry , renin–angiotensin system , antagonist , blood pressure , receptor
Injections of the angiotensin(1–7) [Ang(1–7)] antagonist [ d ‐Ala 7 ]‐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.