PMID- 22889827
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 84
IP  - 8
DP  - 2012 Oct 15
TI  - Nitric oxide-dependent bradycardia in mutant analbuminemic rats.
PG  - 1062-9
LID - S0006-2952(12)00510-2 [pii]
LID - 10.1016/j.bcp.2012.07.028 [doi]
AB  - Nagase analbuminemic rats (NAR) are natural mutant Sprague-Dawley rats which do 
      not express albumin due to a single splice mutation in the albumin gene. We 
      accidentally discovered that NAR have a significant bradycardia compared with 
      wild type Sprague-Dawley rats, and the present study was carried out to 
      investigate the mechanism of bradycardia in analbuminemic rats. In vitro studies 
      showed that the basal spontaneous beating rate of isolated atria is similar in 
      NAR compared with wild type animals. However, the chronotropic responsiveness of 
      isolated atria to cholinergic stimulation was markedly increased in NAR, an 
      effect which was prevented by incubation with a nitric oxide synthase (NOS) or 
      guanylyl cyclase inhibitor. NAR had a significant increase in plasma 
      nitrite/nitrate concentrations. Administration of a NOS inhibitor for 5 days 
      normalized heart rate in NAR. The level of NOS isoforms, caveolin-1 and 
      caveolin-3 expression in the atria was assessed by real time PCR. There was no 
      significant difference in the expression of NOS isoforms or caveolin-3 in NAR 
      compared with wild type controls. However, NAR exhibited a significant decrease 
      in caveolin-1 expression in the atria. Since caveolin-1 is known to inhibit 
      endothelial NOS activity in cardiomyocytes, we suggest that decreased caveolin-1 
      levels may have a role in increased nitric oxide production in NAR. Our data 
      suggest that a NOS/cGMP-dependent mechanism might be involved in increased 
      responsiveness to vagal stimulation and bradycardia in analbuminemic condition.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Mani, Ali R
AU  - Mani AR
AD  - Division of Medicine, UCL Medical School, University College London (UCL), 
      London, UK. rmhaalm@ucl.ac.uk
FAU - Ippolito, Silvia
AU  - Ippolito S
FAU - Centelles, Miguel N
AU  - Centelles MN
FAU - Moore, Kevin P
AU  - Moore KP
LA  - eng
GR  - G0800971/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20120811
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Albumins)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolin 3)
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Inhibitors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Albumins/*analysis
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Western
MH  - Bradycardia/*physiopathology
MH  - Caveolin 1/metabolism
MH  - Caveolin 3/metabolism
MH  - DNA Primers
MH  - Enzyme Inhibitors/pharmacology
MH  - Heart Rate
MH  - Male
MH  - Microscopy, Immunoelectron
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
EDAT- 2012/08/15 06:00
MHDA- 2012/12/14 06:00
CRDT- 2012/08/15 06:00
PHST- 2012/05/27 00:00 [received]
PHST- 2012/07/25 00:00 [revised]
PHST- 2012/07/25 00:00 [accepted]
PHST- 2012/08/15 06:00 [entrez]
PHST- 2012/08/15 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
AID - S0006-2952(12)00510-2 [pii]
AID - 10.1016/j.bcp.2012.07.028 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2012 Oct 15;84(8):1062-9. doi: 10.1016/j.bcp.2012.07.028. Epub 
      2012 Aug 11.