PMID- 16755144
OWN - NLM
STAT- MEDLINE
DCOM- 20060707
LR  - 20171116
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 29
IP  - 2
DP  - 2006 Feb
TI  - Calcium [corrected] channel blockers reduce angiotensin II-induced superoxide 
      generation and inhibit lectin-like oxidized low-density lipoprotein receptor-1 
      expression in endothelial cells.
PG  - 105-16
AB  - Calcium channel blockers have been shown to limit the progression of 
      atherosclerosis and decrease the incidence of cardiovascular events. To 
      investigate vasoprotective effects beyond the blood pressure-lowering effects of 
      these agents, amlodipine (10(-6) mol/) and manidipine (10(-6) mol/l) were used to 
      pretreat angiotensin (Ang) II-stimulated rat cultured aortic endothelial cells. A 
      3-h period of Ang II treatment enhanced superoxide generation and the expression 
      of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein, as 
      detected by dihydroethidium staining and Western blotting, respectively. 
      Pretreatment with amlodipine or manidipine attenuated the increased production of 
      superoxide and the overexpression of NADPH oxidase. The enhanced expression of 
      heme oxygenase-1 (HO-1) mRNA induced by Ang II was further increased by 
      amlodipine, whereas pretreatment with manidipine led to a reduction in the 
      expression of HO-1. Furthermore, Ang II increased vascular cell adhesion 
      molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and monocyte 
      chemoattractant protein-1 (MCP-1) mRNA levels, as determined by reverse 
      transcription (RT)-polymerase chain reaction (PCR). Pretreatment with either 
      amlodipine or manidipine decreased the overexpression of VCAM-1, ICAM-1, and 
      MCP-1. We also demonstrated that amlodipine or manidipine prevented the Ang 
      II-induced increase in lectin-like oxidized low-density lipoprotein receptor1 
      (LOX-1) content, thereby restoring control levels. These observations showed that 
      amlodipine and manidipine reduced superoxide generation by the inhibition of the 
      overexpression of NADPH oxidase in Ang II-stimulated endothelial cells. Such 
      antioxidant effects of these agents might in turn have led to a decrease in the 
      expression of VCAM-1, ICAM-1 and MCP-1. The salutary effects of calcium channel 
      blockers in atherogenesis include the inhibition of the expression of LOX-1.
FAU - Toba, Hiroe
AU  - Toba H
AD  - Department of Clinical Pharmacology, Kyoto Pharmaceutical University, 5 Misasagi 
      Nakauchi-cho, Yamashima-ku, Kyoto 607-8414, Japan. toba@mb.kyoto-phu.ac.jp
FAU - Shimizu, Takahiro
AU  - Shimizu T
FAU - Miki, Shunsuke
AU  - Miki S
FAU - Inoue, Riyako
AU  - Inoue R
FAU - Yoshimura, Akiko
AU  - Yoshimura A
FAU - Tsukamoto, Rie
AU  - Tsukamoto R
FAU - Sawai, Naoki
AU  - Sawai N
FAU - Kobara, Miyuki
AU  - Kobara M
FAU - Nakata, Tetsuo
AU  - Nakata T
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (OLR1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 11062-77-4 (Superoxides)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
EIN - Hypertens Res. 2006 Apr;29(4):295
MH  - Angiotensin II
MH  - Animals
MH  - Aorta/cytology
MH  - Calcium Channel Blockers/*pharmacology
MH  - Cell Adhesion Molecules/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/drug effects
MH  - Endothelial Cells/*drug effects
MH  - Heme Oxygenase-1/drug effects
MH  - Inflammation/metabolism
MH  - Male
MH  - NADPH Oxidases/drug effects
MH  - Oxidative Stress/*drug effects
MH  - RNA, Messenger/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Scavenger Receptors, Class E/*drug effects
MH  - Superoxides/metabolism
EDAT- 2006/06/07 09:00
MHDA- 2006/07/11 09:00
CRDT- 2006/06/07 09:00
PHST- 2006/06/07 09:00 [pubmed]
PHST- 2006/07/11 09:00 [medline]
PHST- 2006/06/07 09:00 [entrez]
AID - JST.JSTAGE/hypres/29.105 [pii]
AID - 10.1291/hypres.29.105 [doi]
PST - ppublish
SO  - Hypertens Res. 2006 Feb;29(2):105-16. doi: 10.1291/hypres.29.105.