PMID- 21864717
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20200508
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Linking)
VI  - 55
IP  - 5-6
DP  - 2011 Nov-Dec
TI  - Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the 
      rat.
PG  - 163-8
LID - 10.1016/j.vph.2011.08.215 [doi]
AB  - The study has been designed to investigate the effect of fenofibrate on 
      nicotine-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 
      mg/kg/day, i.p., 4 weeks) was administered to produce VED in rats. The 
      development of VED was assessed by employing isolated aortic ring preparation and 
      estimating serum and aortic concentration of nitrite/nitrate. Further, the 
      integrity of vascular endothelium was assessed using the scanning electron 
      microscopy of thoracic aorta. The expression of mRNA for p22phox and eNOS was 
      assessed by using reverse transcriptase-polymerase chain reaction. Serum 
      thiobarbituric acid reactive substances concentration (TBARS) and aortic 
      superoxide anion concentration were estimated to assess oxidative stress. 
      Moreover, the serum lipid profile was assessed by estimating serum cholesterol, 
      triglycerides and high density lipoprotein. The administration of nicotine 
      induces VED by increased oxidative stress, altered lipid profile and impaired the 
      integrity of vascular endothelium as assessed in terms of decrease in expression 
      of mRNA for endothelial nitric oxide synthase (eNOS), impairing the integrity of 
      vascular endothelium and subsequently decreasing serum and aortic nitrite/nitrate 
      and attenuating acetylcholine-induced endothelium dependent relaxation. Further, 
      nicotine produced oxidative stress, assessed in terms of increase in serum TBARS 
      and aortic superoxide anion generation and increase in expression of mRNA for 
      p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol, 
      triglycerides and decreasing the high density lipoprotein. However, treatment 
      with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by 
      decreasing oxidative stress and improving integrity of vascular endothelium, 
      normalising the altered lipid profile, increasing the concentration of serum and 
      aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent 
      relaxation and decreasing serum TBARS and aortic superoxide anion generation. 
      Thus, it may be concluded that fenofibrate has vascular protecting potential, by 
      improving the integrity and function of vascular endothelium.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Chakkarwar, Vishal Arvind
AU  - Chakkarwar VA
AD  - Cardiovascular Pharmacology Division, I.S.F. Institute of Pharmaceutical Sciences 
      and Drug Research, Moga 142 001, India. vishalcp1811@gmail.com
LA  - eng
PT  - Journal Article
DEP - 20110816
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Free Radicals)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (RNA, Messenger)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (Cyba protein, rat)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects/metabolism/physiopathology/ultrastructure
MH  - *Disease Models, Animal
MH  - Endothelium, Vascular/*drug effects/metabolism/physiopathology/ultrastructure
MH  - Fenofibrate/*therapeutic use
MH  - Free Radicals/blood/metabolism
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Hyperlipidemias/metabolism/pathology/physiopathology/prevention & control
MH  - Hypolipidemic Agents/*therapeutic use
MH  - Male
MH  - NADPH Oxidases/biosynthesis/genetics/metabolism
MH  - Nicotine
MH  - Nitric Oxide Synthase Type III/biosynthesis/genetics/metabolism
MH  - Oxidative Stress/drug effects
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Surface Properties
MH  - Vascular Diseases/metabolism/pathology/physiopathology/*prevention & control
MH  - Vasodilation/drug effects
EDAT- 2011/08/26 06:00
MHDA- 2013/05/02 06:00
CRDT- 2011/08/26 06:00
PHST- 2010/03/18 00:00 [received]
PHST- 2011/07/31 00:00 [revised]
PHST- 2011/08/08 00:00 [accepted]
PHST- 2011/08/26 06:00 [entrez]
PHST- 2011/08/26 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
AID - S1537-1891(11)00317-X [pii]
AID - 10.1016/j.vph.2011.08.215 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2011 Nov-Dec;55(5-6):163-8. doi: 10.1016/j.vph.2011.08.215. 
      Epub 2011 Aug 16.