Anti-Atherosclerotic Effect of β-Blocker with Nitric Oxide–Releasing Action on the Severe Atherosclerosis

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Abstract
It is not completely understood whether nitric oxide donors and beta-adrenoceptor antagonists have anti-atherosclerotic effects. The anti-atherosclerotic effects of beta-adrenergic receptor antagonists and nitric oxide donors on severe atherosclerosis induced by cholesterol and inhibition of nitric oxide synthesis were determined. Six groups of New Zealand white male rabbits were treated for 10 weeks, under the following regimens: group I: high-cholesterol diet (HCD) (standard diet plus 0.5% cholesterol); group II: HCD plus N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase; group III: HCD plus L-NAME and isosorbide dinitrate; group IV: HCD plus L-NAME and nitroglycerin; group V: HCD plus L-NAME and nipradilol (beta-blocker with nitric oxide-releasing action); and group VI: HCD plus L-NAME and atenolol (beta-blocker). Serum lipid levels did not differ among the six groups. Blood pressure and heart rates were slightly decreased in groups V and VI. The atherosclerotic area and aortic cholesterol increased in L-NAME-treated animals but not in animals in group V. The endothelium-dependent relaxations and basal nitric oxide release were impaired in the L-NAME treatment group, though not in group V, in comparison with those in group I. cGMP in the aorta was increased in groups III, IV, and V as compared with that in group II. Endothelial nitric oxide synthase mRNA was decreased in the aortae of L-NAME-treated rabbits and increased in aortae in group V, in comparison with that in group I. Conclusively, nipradilol, beta-blocker with nitric oxide-releasing action, in contrast to the other beta-blockers and nitric oxide donors, showed a successful anti-atherosclerotic effect through the restoration of nitric oxide bioavailability and possible interaction with oxygen radicals.