[Effects of carvedilol and proxodolol on nitric oxide (NO) metabolism in various organs in a congestive heart failure model].

There is certain evidence that high efficacy of beta-adrenoblockers with alpha-adrenoblocking effect (vasodilating beta-blockers) in congestive heart failure (CHF) can be explained by their effect on nitric oxide (NO) metabolism. In this context, the possible effects of carvedilol and proxodolol on the NO level in different organs have been studied on CHF model. The heart failure was modeled in rats by ligation of the coronary artery. Operated animals were divided into experimental groups treated with carvedilol or proxodolol and the untreated (control) group. In addition, a group of sham-operated animals was formed. After 28 days of treatment, the NO level was measured in heart, liver, and kidneys using the EPR method with spin trap. It was found that, in carvedilol-treated group, the NO level in liver is significantly lower than in other groups, which can be explained by the inhibitory action of carvedilol on the NO metabolism in this organ. The NO levels in myocardium and kidney in the control group were higher than in the sham-operated group, which confirms previous findings that the NO levels increases in CHF. Both drugs significantly decreased the NO concentration in myocardium and kidney tissue compared to control animals.

Chronic administration of coenzyme Q10 limits postinfarct myocardial remodeling in rats.

The effect of chronic coronary artery occlusion on the content of rat myocardial coenzymes Q (CoQ) and evaluation of the applicability of CoQ(10) for limiting postinfarct remodeling have been investigated. Left ventricle myocardium hypertrophy was characterized by the decrease in CoQ(9) (-45%, p < 0.0001), CoQ(10) (-43%, p < 0.001), and alpha-tocopherol (-35%, p < 0.05). There were no differences between the parameters of postinfarction and sham-operated rats in plasma. Administration of CoQ(10) (10 mg/kg) via a gastric probe for 3 weeks before and 3 weeks after occlusion maintained higher levels of CoQ in the postinfarction myocardium: the decrease in CoQ(9) and CoQ(10) was 25% (p < 0.05) and 23% (p < 0.05), respectively (versus sham-operated animals). Plasma concentrations of CoQ(10) were more than 2 times higher (p < 0.05). In CoQ treated rats there was significant correlation between plasma levels of CoQ and the infarct size: r = -0.723 (p < 0.05) and r = -0.839 (p < 0.01) for CoQ(9) and CoQ(10). These animals were also characterized by earlier and more intensive scar tissue formation in the postinfarction myocardium and also by more pronounced cell regeneration processes. This resulted in the decrease in both the infarct size (16.2 +/- 8.1 vs. 27.8 +/- 12.1%) and also mass index of left ventricle (2.18 +/- 0.24 vs. 2.38 +/- 0.27 g/kg) versus untreated rats (p < 0.05). Thus, long-term treatment with ubiquinone increases plasma and myocardial CoQ content and this can improve the survival of myocardial cells during ischemia and limit postinfarct myocardial remodeling.

[Studying the effect of the new beta-adrenoreceptor blocker proxodolol on the ischemic model of cardiac insufficiency].

The effects of proxodolol--new beta-blocker with alpha-blocking activity--on system hemodynamics, heart function and morphology of rats with ischemia-induced congestive heart failure were studied and compared with those of carvedilol. It was shown that both drugs administered during 3 weeks after ligation of coronary artery inhibit heart remodeling and development of myocardial hypertrophy. Proxodolol was more effective than carvedilol in prevention of heart dysfunctions typical for congestive heart failure, that was especially evident during the pharmacological overload tests.