Effects of nitric oxide modulators on cardiovascular risk factors in mild hyperhomocysteinaemic rat model.
Hyperhomocysteinaemia is considered to be an independent risk factor in atherosclerosis. In the present article, we observed the effect of nitric oxide modulators on cardiovascular risk factors in mild hyperhomocysteinaemic rats. A rat model of mild hyperhomocysteinaemia was established by administering methionine (1 g/kg body weight, orally) for 4 weeks. The other groups were concomitantly treated with sodium nitroprusside (SNP) and N(omega)-nitro-l-arginine (LNNA) during the induction of hyperhomocysteinaemia. Lipid profile, total antioxidant capacity and the level of homocysteine and NO(x) (nitrates and nitrites) was examined in serum at 0 and 4 weeks. Activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the mRNA level of caveolin, P2 receptors and cardiovascular risk factors were also analysed. Stimulated lipid profile of rats by the treatment of methionine (1 g/kg body weight) reduced significantly by the treatment of SNP with methionine. LNNA increased the level of cholesterol in aorta (P < 0.05 versus group II). SNP significantly suppressed the activity of HMG-CoA reductase. The mRNA levels of caveolin (P < 0.05), P2X (P < 0.05) and P2Y (P < 0.05) showed a significant decrease in rats administered with SNP. LNNA showed significant induction in the expression of caveolin (P < 0.01) and P2Y (P < 0.01) expression. The level of P2X showed no remarkable change in animals treated with LNNA and methionine both. These data conclude that nitric oxide modulators modulate the effect of hyperhomocysteinaemia on the other cardiovascular risk factors and confirm the finding that nitric oxide plays an important role in homocysteine-induced cardiovascular diseases.
Sharma
Meenakshi
M
Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India. meenakshisha@gmail.com
Rai
Santosh Kr
SK
Tiwari
Rakesh Kr
RK
Tiwari
Manisha
M
Chandra
Ramesh
R
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D051243:Caveolin 2 / Q000096:biosynthesis; D004195:Disease Models, Animal; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000378:metabolism; D015289:Leukotrienes / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008715:Methionine; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis; D052243:Resistin / Q000097:blood; D012307:Risk Factors
D000214:Acyl Coenzyme A; D051243:Caveolin 2; D015289:Leukotrienes; D020030:Nitric Oxide Donors; D018048:Receptors, Purinergic P2; D052243:Resistin; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D002097:C-Reactive Protein; D008715:Methionine