PMID- 23118038
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20130218
IS  - 1752-8976 (Electronic)
IS  - 1470-3203 (Linking)
VI  - 14
IP  - 1
DP  - 2013 Mar
TI  - Aliskiren, at low doses, reduces the electrical remodeling in the heart of the 
      TGR(mRen2)27 rat independently of blood pressure.
PG  - 23-33
LID - 10.1177/1470320312463832 [doi]
AB  - METHODS: The influence of chronic administration of low doses of aliskiren (5 
      mg/kg/day, i.p.) for a period of eight weeks on cardiac electrophysiological and 
      structural remodeling was investigated in transgenic (TGR)(mRen-2)27 rats. 
      Cardiac and plasma angiotensin II (Ang II) levels were determined by ELISA before 
      and after administration of the drug. Moreover, histological, 
      electrophysiological and echocardiographic studies were performed in controls and 
      at the end of eight weeks of aliskiren administration. RESULTS: 1) The cardiac 
      Ang II levels were significantly reduced while the plasma Ang II levels were not 
      significantly decreased in rats treated with low doses of aliskiren; 2) 
      echocardographic studies showed a decrease of left ventricle diameter (LVD), left 
      ventricle posterior wall thickness (LVPW), left ventricle end diastolic volume 
      (LVEDV) and increased ejection fraction (EF); 3) aliskiren improved the impulse 
      propagation, increased the cardiac refractoriness and reduced the incidence of 
      triggered activity; 4) perivascular and interstitial fibrosis were greatly 
      reduced, which explains the increase in conduction velocity. All these effects of 
      aliskiren were found independently of blood pressure, suggesting that the 
      beneficial effect of aliskiren was related to an inhibition of the local cardiac 
      renin angiotensin system; and 5) the effect of mechanical stretch on action 
      potential duration, conduction velocity and spontaneous rhythmicity was changed 
      by aliskiren, supporting the hypothesis presented here that the beneficial effect 
      of the drug on cardiac remodeling is related to a decreased sensitivity of 
      cardiac muscle to mechanical stress.
FAU - De Mello, Walmor
AU  - De Mello W
AD  - School of Medicine, Medical Sciences Campus, University of Puerto Rico, USA. 
      walmor.de-mello@upr.edu
FAU - Rivera, Marielis
AU  - Rivera M
FAU - Rabell, Andres
AU  - Rabell A
FAU - Gerena, Yamil
AU  - Gerena Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121101
PL  - England
TA  - J Renin Angiotensin Aldosterone Syst
JT  - Journal of the renin-angiotensin-aldosterone system : JRAAS
JID - 100971636
RN  - 0 (Amides)
RN  - 0 (Fumarates)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 502FWN4Q32 (aliskiren)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Amides/*administration & dosage/*pharmacology
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Electrocardiography
MH  - Electrophysiological Phenomena/*drug effects
MH  - Fibrosis
MH  - Fumarates/*administration & dosage/*pharmacology
MH  - Heart/drug effects/*physiopathology
MH  - Heart Ventricles/drug effects/pathology/physiopathology
MH  - Male
MH  - Myocardium/pathology
MH  - Rats
MH  - Rats, Transgenic
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Stress, Mechanical
MH  - Systole/drug effects
MH  - Ventricular Remodeling/*drug effects
EDAT- 2012/11/03 06:00
MHDA- 2013/09/21 06:00
CRDT- 2012/11/03 06:00
PHST- 2012/11/03 06:00 [entrez]
PHST- 2012/11/03 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - 1470320312463832 [pii]
AID - 10.1177/1470320312463832 [doi]
PST - ppublish
SO  - J Renin Angiotensin Aldosterone Syst. 2013 Mar;14(1):23-33. doi: 
      10.1177/1470320312463832. Epub 2012 Nov 1.