PMID- 23163825
OWN - NLM
STAT- MEDLINE
DCOM- 20130317
LR  - 20220316
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 124
IP  - 9
DP  - 2013 May
TI  - Do high doses of AT(1)-receptor blockers attenuate central sympathetic outflow in 
      humans with chronic heart failure?
PG  - 589-95
LID - 10.1042/CS20120437 [doi]
AB  - In patients with CHF (chronic heart failure) sympathetic activity increases as 
      cardiac performance decreases and filling pressures increase. We hypothesized 
      that in patients with mild-to-moderate CHF, higher than conventional doses of an 
      AT1-receptor [AngII (angiotensin II) type 1 receptor] antagonist would achieve 
      greater central AT1-receptor blockade, resulting in diminished MSNA (muscle 
      sympathetic nerve activity) and augmented MSNA variability, two indices of 
      central effects on sympathetic outflow. In total, 13 patients with ischaemic 
      cardiomyopathy [NYHA (New York Heart Association) class II-III] were weaned off 
      all pharmacological RAS (renin-angiotensin system) modifiers, and then randomized 
      to receive a low (50 mg/day) or high (200 mg/day) dose of losartan. Central 
      haemodynamics, MSNA and its variability, plasma catecholamines, AngI (angiotensin 
      I) and AngII and aldosterone were assessed both before and 3 months after 
      randomization. Neither dose altered BP (blood pressure), PCWP (pulmonary 
      capillary wedge pressure) or CI (cardiac index) significantly. Compared with 50 
      mg daily, losartan 200 mg/day decreased MSNA significantly (P<0.05), by 
      approximately 15 bursts/min, and increased MSNA variability within the 0.27-0.33 
      Hz high-frequency range by 0.11 units(2)/Hz (P=0.06). PNE [plasma noradrenaline 
      (norepinephrine)] fell in parallel with changes in MSNA (r=0.62; P<0.05). These 
      findings support the hypothesis that higher than conventional doses of lipophilic 
      ARBs (AT1-receptor blockers) can modulate the intensity and variability of 
      central sympathetic outflow in patients with CHF. The efficacy and safety of this 
      conceptual change in the therapeutic approach to heart failure merits prospective 
      testing in clinical trials.
FAU - Ruzicka, Marcel
AU  - Ruzicka M
AD  - Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, 
      Canada. mruzicka@ottawahospital.on.ca
FAU - Floras, John S
AU  - Floras JS
FAU - McReynolds, Andrew J G
AU  - McReynolds AJ
FAU - Coletta, Elizabeth
AU  - Coletta E
FAU - Haddad, Haissam
AU  - Haddad H
FAU - Davies, Ross
AU  - Davies R
FAU - Leenen, Frans H H
AU  - Leenen FH
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 4964P6T9RB (Aldosterone)
RN  - JMS50MPO89 (Losartan)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Aldosterone/blood
MH  - Angiotensin II Type 1 Receptor Blockers/*therapeutic use
MH  - Female
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Humans
MH  - Losartan/*administration & dosage/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Norepinephrine/blood
MH  - Sympathetic Nervous System/drug effects/physiopathology
EDAT- 2012/11/21 06:00
MHDA- 2013/03/19 06:00
CRDT- 2012/11/21 06:00
PHST- 2012/11/21 06:00 [entrez]
PHST- 2012/11/21 06:00 [pubmed]
PHST- 2013/03/19 06:00 [medline]
AID - CS20120437 [pii]
AID - 10.1042/CS20120437 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2013 May;124(9):589-95. doi: 10.1042/CS20120437.