Document Detail

Changes in the baroreflex control of heart rate produced by central infusion of selective angiotensin antagonists in hypertensive rats.
MedLine Citation:
PMID:  8641737     Owner:  NLM     Status:  MEDLINE    
We have recently shown that an angiotensin-(1-7) [Ang-(I-7)] analogue, D-Ala7-Ang-(1-7) (A-779), is a selective Ang-(1-7) antagonist with no significant action on angiotensin type 1 or type 2 receptors. The availability of selective angiotensin antagonists prompted us to evaluate the role of Ang-(1-7) and Ang II on central modulation of the baroreflex control of heart rate in normotensive Wistar rats and spontaneously hypertensive rats (SHR). Blood pressure recording and reflex changes in heart rate elicited by intravenous bolus injections of phenylephrine were made before and within 1 and 3 hours of intracerebroventricular (ICV, lateral ventricle) infusion of saline (8 microL/h), A-779 (4 microg/h), DuP 753 (100 microg/h), or CGP 42112A (50 mu g/h) in conscious rats. The slope of the relationship between changes in pulse interval versus changes in mean arterial pressure was used as an index of the baroreflex control of heart rate. ICV infusion of saline or any of the antagonists did not significantly change basal levels of mean arterial pressure and heart rate in SHR (170 +/- 6 mm Hg nd 360 +/- 9 beats per minute, respectively; n = 29) or Wistar rats (108 +/- 2 mm Hg and 377 +/- 6 beats per minute, respectively; n=29). Three hours of ICV infusion of A-779 markedly decreased baroreflex sensitivity in Wistar rats (from a basal slope of 1.09 +/- O.3). In contrast, A-779 did not significantly alter the depressed baroreflex sensitivity of SHR (0.61 +/- O.l). ICV infusion of DuP 753 produced a significant increase (60 percent) in baroreflex control of heart rate in both Wistar rats and SHR. Saline or CGP 42112A infusions did not significantly alter baroreflex control of heart rate. These results suggest that endogenous Ang II and Ang-(1-7) are differentially affecting central baroreflex modulation, acting probably through distinct receptor subtypes. Although the central Ang II inhibitory effect is mediated by the type 1 receptor subtype, the facilitatory effect of Ang-(1-7) might be mediated by a different, unidentified receptor.
D R Oliveira; R A Santos; G F Santos; M Khosla; M J Campagnole-Santos
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  27     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-07-18     Completed Date:  1996-07-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1284-90     Citation Subset:  IM    
Laboratório de Hipertensão, Departamento de Fisiologia and Biofísica,Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
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MeSH Terms
Angiotensin II / analogs & derivatives,  antagonists & inhibitors*,  pharmacology
Antihypertensive Agents / pharmacology*
Baroreflex / drug effects*
Biphenyl Compounds / pharmacology
Heart Rate / drug effects*
Imidazoles / pharmacology
Oligopeptides / pharmacology
Peptide Fragments / pharmacology
Rats, Inbred SHR
Rats, Inbred WKY
Tetrazoles / pharmacology
Reg. No./Substance:
0/7-Ala-angiotensin (1-7); 0/Antihypertensive Agents; 0/Biphenyl Compounds; 0/Imidazoles; 0/Oligopeptides; 0/Peptide Fragments; 0/Tetrazoles; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 127060-75-7/CGP 42112A

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