Document Detail


Angiotensin-converting enzyme inhibition, but not AT(1) receptor blockade, in the solitary tract nucleus improves baroreflex sensitivity in anesthetized transgenic hypertensive (mRen2)27 rats.
MedLine Citation:
PMID:  21937997     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Transgenic hypertensive (mRen2)27 rats overexpress the murine Ren2 gene and have impaired baroreflex sensitivity (BRS) for control of the heart rate. Removal of endogenous angiotensin (Ang)-(1-7) tone using a receptor blocker does not further lower BRS. Therefore, we assessed whether blockade of Ang II with a receptor antagonist or combined reduction in Ang II and restoration of endogenous Ang-(1-7) levels with Ang-converting enzyme (ACE) inhibition will improve BRS in these animals. Bilateral solitary tract nucleus (nTS) microinjections of the AT(1) receptor blocker, candesartan (CAN, 24 pmol in 120 nl, n=9), or a peptidic ACE inhibitor, bradykinin (BK) potentiating nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro; BPP9α, 9 nmol in 60 nl, n=12), in anesthetized male (mRen2)27 rats (15-25 weeks of age) show that AT(1) receptor blockade had no significant effect on BRS, whereas microinjection of BPP9α improved BRS over 60-120 min. To determine whether Ang-(1-7) or BK contribute to the increase in BRS, separate experiments using the Ang-(1-7) receptor antagonist D-Ala(7)-Ang-(1-7) or the BK antagonist HOE-140 showed that only the Ang-(1-7) receptor blocker completely reversed the BRS improvement. Thus, acute AT(1) blockade is unable to reverse the effects of long-term Ang II overexpression on BRS, whereas ACE inhibition restores BRS over this same time frame. As the BPP9α potentiation of BK actions is a rapid phenomenon, the likely mechanism for the observed delayed increase in BRS is through ACE inhibition and elevation of endogenous Ang-(1-7).Hypertension Research advance online publication, 22 September 2011; doi:10.1038/hr.2011.110.
Authors:
Katsunori Isa; Amy C Arnold; Brian M Westwood; Mark C Chappell; Debra I Diz
Related Documents :
22448217 - Dynamic 5-ht2c receptor editing in a mouse model of obesity.
18223557 - Wild-type and splice-variant secretin receptors in lung cancer: overexpression in carci...
9117097 - Somatostatin receptors in neuro2a neuroblastoma cells: operational characteristics.
21330367 - Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insul...
10773037 - Toward development of an in vitro model of methamphetamine-induced dopamine nerve termi...
1671087 - Multiple adrenergic receptor subtypes controlling cyclic amp formation: comparison of b...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-22
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  -     ISSN:  1348-4214     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Responses of the second derivative of the finger photoplethysmogram indices and hemodynamic paramete...
Next Document:  Single-nucleotide polymorphisms at five loci are associated with C-reactive protein levels in a coho...