PMID- 16392774
OWN - NLM
STAT- MEDLINE
DCOM- 20060131
LR  - 20211203
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 28
IP  - 8
DP  - 2005 Aug
TI  - Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by 
      augmentation of endothelial nitric oxide synthase and the inhibition of 
      angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced 
      hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering 
      effects of amlodipine and manidipine.
PG  - 689-700
AB  - Long-acting dihydropyridine calcium channel blockades have been shown to limit 
      the progression of atherosclerosis and decrease the incidence of cardiovascular 
      events in humans and animals. To investigate the vasoprotective effects beyond 
      the blood pressure-lowering effects of these agents, amlodipine (20 mg/kg/ day) 
      and manidipine (10 mg/kg/day) were administered by gavage to 
      N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats for 2 
      weeks. L-NAME treatment (0.7 mg/ml in drinking water) significantly decreased the 
      gene and protein expression of endothelial nitric oxide synthase (eNOS) and 
      increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, vascular 
      cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) 
      mRNA levels in the aorta, as determined by Western blotting and reverse 
      transcription (RT)-polymerase chain reaction (PCR). Amlodipine and manidipine 
      normalized the decreased expression of eNOS gene and protein, and attenuated the 
      overexpression of NADPH oxidase, VCAM-1, and MCP-1 mRNA. Furthermore, amlodipine 
      and manidipine prevented the L-NAME-induced increase in the angiotensin 
      converting enzyme (ACE) mRNA content, thereby restoring control levels in the 
      aorta. On the other hand, hydralazine treatment had no such effect in L-NAME 
      treated rats. Furthermore, the increased expression of manganese superoxide 
      dismutase (Mn-SOD) by L-NAME treatment was not affected by amlodipine, 
      manidipine, or hydralazine. We concluded that the direct anti-inflammatory and 
      antioxidative effects of calcium channel blockades in the aorta of rats with 
      L-NAME-induced hypertension were not likely to have been mediated by the blood 
      pressure-lowering action of these agents, but instead these beneficial effects 
      appear to have been mediated by an augmentation of eNOS expression and by the 
      inhibition of the expression of ACE.
FAU - Toba, Hiroe
AU  - Toba H
AD  - Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, 
      Japan. toba@mb.kyoto-phu.ac.jp
FAU - Nakagawa, Yoshitsugu
AU  - Nakagawa Y
FAU - Miki, Shunsuke
AU  - Miki S
FAU - Shimizu, Takahiro
AU  - Shimizu T
FAU - Yoshimura, Akiko
AU  - Yoshimura A
FAU - Inoue, Riyako
AU  - Inoue R
FAU - Asayama, Jun
AU  - Asayama J
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 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dihydropyridines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrobenzenes)
RN  - 0 (Piperazines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 1J444QC288 (Amlodipine)
RN  - 6O4754US88 (manidipine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Amlodipine/pharmacology
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antihypertensive Agents/pharmacology
MH  - Antioxidants/*pharmacology
MH  - Aorta/chemistry/*enzymology/physiology
MH  - Blood Pressure/drug effects/physiology
MH  - Body Weight/physiology
MH  - Calcium Channel Blockers/*pharmacology
MH  - Chemokine CCL2/analysis/genetics
MH  - Dihydropyridines/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Heart Rate/drug effects/physiology
MH  - Hypertension/chemically induced/*enzymology/physiopathology
MH  - Inflammation/physiopathology
MH  - Male
MH  - NADPH Oxidases/analysis/genetics
MH  - NG-Nitroarginine Methyl Ester
MH  - Nitric Oxide Synthase Type III/genetics/*metabolism
MH  - Nitrobenzenes
MH  - Oxidative Stress/drug effects
MH  - Peptidyl-Dipeptidase A/analysis/genetics
MH  - Piperazines
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Vascular Cell Adhesion Molecule-1/analysis/genetics
EDAT- 2006/01/06 09:00
MHDA- 2006/02/01 09:00
CRDT- 2006/01/06 09:00
PHST- 2006/01/06 09:00 [pubmed]
PHST- 2006/02/01 09:00 [medline]
PHST- 2006/01/06 09:00 [entrez]
AID - 10.1291/hypres.28.689 [doi]
PST - ppublish
SO  - Hypertens Res. 2005 Aug;28(8):689-700. doi: 10.1291/hypres.28.689.