Increased superoxide radical with a decrease in vascular endothelial growth factor and inducible nitric oxide synthase level leads to the progression of left ventricular hypertrophy in a pressure-overload rat heart model.
OBJECTIVE
This study was designed to evaluate the relationship among free radicals and vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) during the progression of left ventricular hypertrophy (LVH) in pressure-overload rat heart.


METHODS
Hypertrophied rat heart created by abdominal aortic banding at the age of 4 weeks was studied at the ages of 14, 15, 18, 21, 26, and 30 weeks (n=5 in each group). Free radicals were detected by an electron spin resonance (ESR) method using LV tissue. The levels of messenger ribonucleic acid (mRNA) for VEGF, superoxide dismutase (SOD), and iNOS in myocardium were analyzed by reverse transcription (RT)-polymerase chain reaction (PCR).


RESULTS
Free radicals consisting of superoxide families increased over time after aortic banding and were highest in the 30-week group. The SOD mRNA level decreased with the progression of hypertrophy and was inversely proportional to the free radicals level. As compared to the control, the level of mRNA for VEGF and iNOS was significantly increased in 18-and 21-week hypertrophied hearts, but significantly decreased in 26-and 30-week hearts.


CONCLUSIONS
The increased level of free radicals with the decrease of VEGF and iNOS levels may contribute to the progression of the pressure-overload hypertrophied heart to the failing heart.
Ji
Kaiqiang
K
Department of Thoracic and Cardiovascular Surgery, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
Minakawa
Masahito
M
Fukui
Kozo
K
Suzuki
Yasuyuki
Y
Fukuda
Ikuo
I
D000818:Animals; D001011:Aorta / Q000601:surgery; D001794:Blood Pressure; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D004578:Electron Spin Resonance Spectroscopy; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013481:Superoxides; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase