Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.
BACKGROUND
Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated.


METHODS
Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment.


RESULTS
No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy.


CONCLUSIONS
Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy.
Department of Cardiology, Yantaishan Hospital, Yantai, Shandong Province, China.
Fang
F
Yang
Department of General Surgery, Yeda Hospital, Yantai, Binzhou Medical College, Shandong Province, China.
Jindong
J
Wang
Department of Cardiology, Yantaishan Hospital, Yantai, Shandong Province, China.
Fei
F
Li
Department of Cardiology, Yeda Hospital, Yantai, Binzhou Medical College, Shandong Province, China.
Lei
L
Cui
D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000069059:Atorvastatin; D054460:rho-Associated Kinases; D005996:Nitroglycerin