[show abstract][hide abstract] ABSTRACT: The renin-angiotensin-aldosterone system (RAAS) determines progression of heart failure (HF) in humans, and RAAS inhibition is a major therapeutic strategy in HF.
To assess the effect of angiotensin-converting enzyme inhibitor (ACE-I) and aldosterone receptor antagonist (ARA) therapy on the development of HF at its early and late stage in a murine model of dilated cardiomyopathy (Tgaq*44 mice).
Tgaq*44 mice at the early or advanced stage of HF received combined therapy including ACE-I (perindopril 2 mg/kg) and ARA (canrenone 20 mg/kg). Cardiac function was assessed by magnetic resonance imaging before and after 2 months of treatment.
Combined therapy with perindopril and canrenone resulted in preserved systolic function at the early stage and reduced chamber dilatation at the advanced stage of HF in Tgaq*44 mice.
Activation of the RAAS is involved in progression of HF in Tgaq*44 mice with dilated cardiomyopathy. Therapeutic efficacy of ACE-I and ARA to inhibit systolic dysfunction and cardiac chamber dilation depends on the stage of HF development.
Kardiologia polska 01/2013; 71(7):730-7. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although in apoE/LDLR(-/-) mice atherosclerotic plaques develop spontaneously, various atherogenic diets (e.g. Western diet) are frequently used to accelerate the disease in this model. The objective of this study was to compare the effects on atherosclerosis of Western diet and other types of high-fat, high cholesterol, hypertriglyceridemic diets with the effects of the low carbohydrate, high protein (LCHP) diet. 16-18 week old mice with pre-established atherosclerosis were assigned to experimental groups and fed for the next 10 weeks with control diet, margarine diet (margarine 7%), hypertrigliceridemic diet (fructose 62%), high-fat diet (Western diet), high cholesterol diet (egg yolk diet) or with LCHP diet. No differences in body weight were observed among experimental groups. Plasma cholesterol concentration was significantly increased in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice as compared to other types of diets. Plasma concentration of triacylglycerols was significantly elevated in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice. The area of atherosclerotic plaques in the aortic root was substantially increased in LCHP diet-fed mice as compared to other types of diets. Furthermore, in brachiocephalic arteries of LCHP diet-fed mice there was evidence of plaque rupture. In conclusion, the LCHP diet promoted atherosclerosis in apoE/LDLR(-/-) mice more intensively than classical Western diet and favored the development of unstable lesions.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to evaluate functional effects of margarine supplemented with individual CLA isomers trans-10, cis-12 and cis-9, trans-11 in apoE/LDLR -/- mice.
In LONG experiment (LONG), two-month old mice with no atherosclerosis were assigned to experimental groups and fed for the next 4 months. In SHORT experiment (SHORT), four-month old mice, with pre-established atherosclerosis, were assigned to experimental groups and fed for the next 2 months. The experimental diets were: AIN-93G (margarine), AIN-93G + 0.5% trans-10, cis-12 CLA (t10c12), and AIN-93G + 0.5% cis-9, trans-11 CLA (c9t11).
In both experiments (LONG and SHORT), liver weight was significantly (P<0.05) increased in mice fed t10c12 CLA. Hepatic steatosis was found in animals fed t10c12 diet and no signs of the steatosis was observed in mice fed c9t11 CLA. Dietary treatments with t10c12 CLA significantly increased total plasma cholesterol and plasma triacylglycerols. There were no isomer-specific effects of CLA isomers on area of atherosclerotic plaque in aortic root.
In conclusion, t10c12 CLA significantly increased liver weight in mice in LONG and SHORT experiments. Our results do not support the notion that CLA isomer supplementation to the margarine possess anti-atheroclerotic effect. Therefore, no isomer-specific effects of CLA on development of atherosclerosis were observed.
The Journal of Nutrition Health and Aging 05/2012; 16(5):482-90. · 2.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Methylnicotinamide (MNA) displays vasoprotective activity, however, the regulation of the activity of nicotinamide-N-methyltransferase (NNMT), is largely unknown. We analyze a possible involvement of IL-6 in the activation of NNMT-MNA pathway during an endurance exercise.
FVB, C57Bl/6J IL6(+/+) and C57Bl/6J IL-6(-/-) mice were subjected to the single bout of endurance exercise consisting of 90 min of swimming. Thereafter, exercise-induced changes in NNMT activity in the liver as well as concomitant changes in the concentration of MNA and its further metabolites in plasma were analyzed.
In two strains of mice (FVB and C57Bl/6J IL6(+/+)) 90 min of swimming resulted in approximately 2-3 folds increase in NNMT activity (from 0.14 ± 0.03 to 0.421 ± 0.02 pmol/min/mg, p < 0.05 and from 0.2 ± 0.06 to 0.35 ± 0.07 pmol/min/mg, p < 0.01, respectively) and concomitant increase in the plasma concentration of MNA (from 157 ± 15.06 to 230 ± 16.2 ng/ml, p < 0.01, and from 77.05 ± 14.6 ng/ml to 152.55 ± 58.4 ng/ml; p < 0.01, respectively). However, in C57Bl/6J IL-6(-/-) mice 90 min of swimming did not change liver NNMT activity (from 0.25 ± 0.07 to 0.23 ± 0.06 pmol/min/mg), while MNA concentration in plasma rose approximately two-fold (from 65.3 ± 30.9 ng/ml to 124.8 ± 35.8 ng/ml; p < 0.05).
We demonstrated for the first time that NNMT - MNA pathway is activated by a single bout of endurance exercise. Interestingly, exercise-induced activation of NNMT in the liver involves IL-6, while the rise in MNA concentration in plasma was partially IL-6-independent. Taking into the consideration the pharmacological activity of MNA, IL-6-dependent and IL-6-independent activation of NNMT, may contribute to the exercise capacity. The physiological role of NNMT in the exercise warrant further studies.
[show abstract][hide abstract] ABSTRACT: Atherosclerosis is a multietiological inflammatory disease of large and medium-sized arteries of increasing incidence in westernized countries. The aim of this study was to identify the biochemical changes during the progression of atherosclerosis by synchrotron radiation Fourier transform infrared microspectroscopy in atheromas of apoE/LDLR¡=¡ mice fed egg-rich diet supplemented or not with angiotensin converting enzyme inhibitor perindopril. Synchrotron radiation Fourier transform infrared microspectroscopy technique was used to obtain information at high spatial resolution about the distribution of proteins (C–N, N–H, CO for amide I and amide II bands), lipids (CH2, CH3 bands) as well as mineral deposits (calcium carbonates and phosphates). Total contents of lipids and proteins were found to be significantly lower in animals treated with the diet and perindopril. An increase in saturation level of lipids was observed in animals fed with egg-rich diet when compared to the normal diet and perindopril treatment, which did not inhibit this effect. Moreover, a significant change in the secondary structure of proteins (ratio between absorption bands 1634 cm-1/1656 cm-1 attributed to beta-type and alfa-type, respectively) was observed in both experimental groups in comparison with the control. Principal component analysis was used to analyse the recorded spectra. It has revealed that higher content of phosphates (wavenumber range 950–1020 cm-1) was observed between egg-rich diet fed animals and the control group.
Acta Physica Polonica Series a 02/2012; 121(2):555-560. · 0.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Taking advantage of the unique model of slowly developing dilated cardiomyopathy in mice with cardiomyocyte-specific transgenic overexpression of activated Gαq protein (Tgαq*44 mice) we analyzed the contribution of the cardiomyocyte malfunction, fibrosis and cytoskeleton remodeling to the development of heart failure in this model. Left ventricular (LV) in vivo function, myocardial fibrosis, cytoskeletal proteins expression and distribution, Ca(2+) handling and contractile function of isolated cardiomyocytes were evaluated at the stages of the early, compensated, and late, decompensated heart failure in 4-, 12- and 14-month-old Tgαq*44 mice, respectively, and compared to age-matched wild-type FVB mice. In the 4-month-old Tgαq*44 mice significant myocardial fibrosis, moderate myocyte hypertrophy and increased expression of regularly arranged and homogenously distributed desmin accompanied by increased phosphorylation of desmin chaperone protein, αB-crystallin, were found. Cardiomyocyte shortening, Ca(2+) handling and LV function were not altered. At 12 and 14 months of age, Tgαq*44 mice displayed progressive deterioration of the LV function. The contractile performance of isolated myocytes was still preserved, and the amplitude of Ca(2+) transients was even increased probably due to impairment of Na(+)/Ca(2+) exchanger function, while fibrosis was more extensive than in younger mice. Moreover, substantial disarrangement of desmin distribution accompanied by decreasing phosphorylation of αB-crystallin appeared. In Tgαq*44 mice disarrangement of desmin, at least partly related to inadequate phosphorylation of αB-crystallin seems to be importantly involved in the progressive deterioration of contractile heart function.
Journal of Molecular and Cellular Cardiology 01/2012; 52(5):978-87. · 5.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of our studies was to verify the potential health-related, anti-atherogenic potency of CLA isomers, fed to apolipoprotein E and LDL receptor double knockout mice (apoE/LDLR−/−), representing a reliable model of atherogenesis. Additionally, the effect of CLA isomers on liver steatosis was observed. In a “long experiment” (LONG), 2-month-old mice with no atherosclerosis were randomly assigned to three experimental groups and fed for the next 4 months. In a “short experiment” (SHORT), 4-month-old mice, with pre-established atherosclerosis, were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: AIN-93G (control), AIN-93G + 0.5% trans-10,cis-12 CLA (t10,c12), and AIN-93G + 0.5% cis9,trans-11 CLA (c9,t11). In both experiments, c9,t11 CLA increased mice body weight. In mice fed t10,c12 CLA weight of liver was threefold (p<0.05) increased what was linked with hepatic steatosis observed in LONG and SHORT experiment. In LONG experiment, t10,c12 CLA significantly (p<0.05) increased plasma TAGs, whereas no such effect was observed in SHORT one. In mice receiving the CLA isomers the level of PPARα and SREBP-1 mRNA in liver were significantly decreased. The expression of their target genes like ACO (PPARα) or FAS (SREBP-1) were not changed. Only c9,t11 increased ACO level in LONG experiment. There were no isomer-specific effects of CLA isomers on the area of atherosclerotic plaque. In conclusion, our results do not support the notion that CLA isomers supplementation to the diet has anti-atherosclerotic effects. CLA isomers have no effect on atherosclerosis in apoE/LDLR−/− mice.Practical applications: CLAs have been shown to occur naturally in food. In the last 10 years, attempts have been made to enrich animal-derived foods in CLA isomers through animal nutrition strategies. Indeed, these attempts resulted in production of functional food such as CLA-enriched milk (butter and cheese), ruminant and non-ruminant meat, as well as eggs. In addition to natural foodstuff, dietary CLA supplements can also contribute to CLA intake in humans. Commercial CLA preparations, fed to laboratory animals, showed several health-related properties, including anti-adipogenic, anti-carcinogenic, anti-atherogenic, and anti-inflammatory effects. The underlying mechanisms of action, however, are only poorly understood. The major objective of our studies was to verify the potential health-related, namely anti-atherogenic potency of CLA isomers, fed to apoE/LDLR−/− mice, representing unique and reliable model of atherogenesis. Additionally, effect of CLA isomers on steatosis was observed.
European Journal of Lipid Science and Technology 02/2011; 113(5):572 - 583. · 2.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: A sensitive and specific liquid chromatography tandem mass spectrometry method with electrospray ionization for the determination of endothelin-1 in rat plasma and lung effluents has been developed and validated. Detection was achieved by an Applied Biosystems MDS Sciex API 2000 triple quadrupole mass spectrometer coupled to an Agilent 1100 LC system. The limit of detection and the limit of the quantification of ET-1 in matrix buffer was estimated at 40 pM and 1 nM, respectively. The precision and accuracy for both intra- and inter-day determination of the analyte ranged from 2.5% to 14.7% and from 104.2% to 113.3%, respectively. No significant relative matrix effect was observed. Stability of ET-1 established in a bench-top, autosampler, long-term storage stability as well as freeze/thaw cycles shown no significant degradation products in the samples. The results of the method validation indicated that this method is applicable for the determination of the ET-1 concentration in an effluent from the isolated lung preparation as well as in vivo in plasma samples to evaluate ET-1 as a potential biomarker of the progression of pulmonary endothelial dysfunction and pulmonary hypertension in rats induced by a monocrotaline injection.
[show abstract][hide abstract] ABSTRACT: Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR−/−) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR−/− mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.
Radiation Physics and Chemistry 01/2010; · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The impairment of cardiac diastolic function is essential for the development and progression of heart failure, regardless of the systolic performance of the heart. Novel methods of diagnosis of diastolic dysfunction in experimental animals are needed in order to validate the effectiveness of novel heart failure treatment.
The in vivo characterisation of diastolic and systolic function of the heart during heart failure progression in Tgalphaq*44 mice using magnetic resonance imaging (MRI) and original image analysis.
Cardiac function in vivo in both Tgalphaq*44 and FVB mice was analysed using MRI at 4.7 T. Magnetic resonance imaging was performed using an ECG triggered fast gradient echo (cine-like flow compensated FLASH) sequence. For the assessment of left ventricle (LV) dynamics at least 20 images per cardiac cycle were acquired in the midventricular short-axis projection at the level of papillary muscles. End-systolic (ESA) and end-diastolic (EDA) areas were estimated from the minimum and maximum values found in the area-time plot. Fractional area change (FAC) defined as (EDA-ESA)/EDA, ejection (ER) and filling (FR) rates defined as slope of the beginning part of the systolic and diastolic limbs were calculated. In addition, heart failure progression in Tgalphaq*44 mice was assessed by morphometric parameters (ventricular weight to body weight index and wet to dry lung weight index), level of BNP mRNA expression as well as survival.
Systolic function assessed by FAC% and ER was stable but slightly impaired up to 10 months of age in Tgalphaq*44 mice as compared to the FVB mice. After 12 months of age of the Tgalphaq*44 mice there was a progressive deterioration of systolic function (ER at 10, 12, 14 months of age were 0.0188 +/- 0.00434, 0.0140 +/- 0.00474, 0.0115 +/- 0.00469 1/ms, respectively). Diastolic function of the Tgalphaq*44 hearts was preserved or even slightly augmented between 4 and 10 months of age, then at the age of 12 months and later profoundly impaired (FR at 10, 12, 14 months of age were 0.0280 +/- 0.01031, 0.0196 +/- 0.01050, 0.0158 +/- 0.00833 1/ms, respectively).
The MRI allows reliable in vivo assessment of the systolic and diastolic function in Tgalphaq*44 mice. In Tgalphaq*44 mice after few months of stable and compensated phase of the heart failure decompensation develops that involves impairment of both systolic and diastolic and leads to the fully symptomatic dilated cardiomyopathy. The precise molecular mechanisms of the systolic and diastolic dysfunction and their relative contribution to the heart failure progression in Tgalphaq*44 mice remain to be established.
Kardiologia polska 05/2009; 67(4):386-95. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nicotinamide N-methyltrasferase (NMMT) catalyzes the conversion of nicotinamide (NA) to 1-methylnicotinamide (MNA). Recent studies have reported that exogenous MNA exerts anti-thrombotic and anti-inflammatory activity, suggesting that endogenous NMMT-derived MNA may play a biological role in the cardiovascular system. In the present study, we assayed changes in hepatic NNMT activity and MNA plasma levels along the progression of atherosclerosis in apoE/LDLR(-/-) mice, as compared to age-matched wild-type mice. Atherosclerosis progression in apoE/LDLR(-/-) mice was quantified in aortic root, while hepatic NNMT activity and MNA plasma concentrations were concomitantly measured in 2-, 3-, 4-, and 6-month-old mice. In apoE/LDLR(-/-) mice, atherosclerotic plaques developed in the aortic roots beginning at the age of 3 months and gradually increased in size, macrophage content, and inflammation intensity over time, as detected by Oil-Red O staining, CD68 immunostaining, and in situ zymography (MMP2/MMP9 activity). Hepatic NNMT activity was upregulated approximately two-fold in apoE/LDLR(-/-) mice by the age of 2 months, as compared to wild-type mice (1.03 +/- 0.14 vs. 0.64 +/- 0.23 pmol/min/mg, respectively). MNA plasma concentrations were also elevated approximately two-fold (0.30 +/- 0.13 vs. 0.17 +/- 0.04 micromol/l, respectively). As atherosclerosis progressed, hepatic NMMTactivity and MNA plasma concentrations increased five-fold in 6-month-old apoE/LDLR(-/-) mice at the stage of advanced atherosclerotic plaques (NMMT activity: 2.29 +/- 0.34 pmol/min/mg, MNA concentration: 1.083 +/- 0.33 micromol/l). In summary, the present study demonstrated that the progression of vascular inflammation and atherosclerosis was associated with the upregulation of hepatic NNMT activity and subsequent increase in endogenous MNA plasma levels. Given the anti-thrombotic and anti-inflammatory properties of exogenous MNA, robust activation of an endogenous NA-MNA pathway in atherosclerosis may play an important compensatory role.
[show abstract][hide abstract] ABSTRACT: Mechanical and biochemical alterations were investigated in permeabilized cardiomyocytes along with the progression of dilated cardiomyopathy (DCM) in a transgenic mouse line overexpressing the activated Galphaq protein (Tgalphaq*44). The isometric force, its Ca(2+) sensitivity (pCa(50)) and the turnover rate of the actin-myosin cycle (k(tr)) were determined at sarcomere lengths (SLs) of 1.9 mum and 2.3 mum before (at 4 and 10 months of age) and after hemodynamic decompensation (at 14 and 18 months of age) in Tgalphaq*44 cardiomyocytes and in age-matched control cardiomyocytes. The SL-dependence of pCa(50) was not different in Tgalphaq*44 and control hearts. In contrast, a significant increase in pCa(50) was observed in the Tgalphaq*44 cardiomyocytes (DeltapCa(50): 0.10-0.15 vs. the controls) after 10 months of age that could be diminished by exposures to the catalytic subunit of protein kinase A (PKA). Accordingly, a decline in endogenous PKA activity and decreased troponin I phosphorylation were detected after 10 months in the Tgalphaq*44 hearts. Finally, the maximal Ca(2+)-activated force (F(o)) and k(tr) were lower and the passive force (F(passive)) was higher at 18 months in the Tgalphaq*44 cardiomyocytes compared to the control. These mechanical alterations were paralleled by a robust increase in beta-myosin heavy chain expression in the Tgalphaq*44 hearts. In conclusion, our data suggested that an initial decrease of PKA signaling and subsequent changes in myofilament protein expression may contribute to the development of dilated cardiomyopathy in Tgalphaq*44 hearts.
Journal of Molecular and Cellular Cardiology 10/2008; 45(3):363-72. · 5.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study we have evaluated the effect of maximal incremental cycling exercise (IE) on the systemic release of prostacyclin (PGI(2)), assessed as plasma 6-keto-PGF(1alpha) concentration in young healthy men. Eleven physically active - untrained men (mean +/- S.D.) aged 22.7 +/- 2.1 years; body mass 76.3 +/- 9.1 kg; BMI 23.30 +/- 2.18 kg . m(-2); maximal oxygen uptake (VO(2max)) 46.5 +/- 3.9 ml . kg(-1) . min(-1), performed an IE test until exhaustion. Plasma concentrations of 6-keto-PGF(1alpha), lactate, and cytokines were measured in venous blood samples taken prior to the exercise and at the exhaustion. The net exercise-induced increase in 6-keto-PGF(1alpha) concentration, expressed as the difference between the end-exercise minus pre-exercise concentration positively correlated with VO(2max) (r=0.78, p=0.004) as well as with the net VO(2) increase at exhaustion (r=0.81, p=0.003), but not with other respiratory, cardiac, metabolic or inflammatory parameters of the exercise (minute ventilation, heart rate, plasma lactate, IL-6 or TNF-alpha concentrations). The exercise-induced increase in 6-keto-PGF(1alpha) concentration?? was significantly higher (p=0.008) in a group of subjects (n=5) with the highest VO(2max) when compared to the group of subjects with the lowest VO(2max), in which no increase in 6-keto-PGF(1alpha) concentration was found. In conclusion, we demonstrated, to our knowledge for the first time, that exercise-induced release of PGI(2) in young healthy men correlates with VO(2max), suggesting that vascular capacity to release PGI(2) in response to physical exercise represents an important factor characterizing exercise tolerance. Moreover, we postulate that the impairment of exercise-induced release of PGI(2) leads to the increased cardiovascular hazard of vigorous exercise.
Physiological research / Academia Scientiarum Bohemoslovaca 05/2008; 58(2):229-38. · 1.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neutrophils and platelets circulate in blood system and play important physiological roles as part of immunological system. Neutrophils are the first line of host defense against various intruders, and platelets are satellite cells cooperating with other components of defense system. Recent studies report about the cooperation among these types of cells. We analyzed the effect of platelets on oxygen burst in neutrophils triggered by Staphylococcus aureus and Escherichia coli bacteria in vitro. The effect of platelets on oxygen burst in neutrophils was measured by luminol enhanced chemiluminescence. Opsonized and non-opsonized bacteria were used as activators. Activation of neutrophils with live non-opsonized and opsonized bacteria in the presence of platelets increased the oxygen burst as compared to the same system without platelets. The gram-positive bacteria (Staphylococcus aureus) were causing higher activation than gram-negative bacteria (Escherichia coli). This work demonstrate that platelets potentate the response of neutrophils augmenting their respiratory burst in vitro when triggered by bacteria.
Folia Histochemica et Cytobiologica 02/2008; 46(3):383-8. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.
Folia Histochemica et Cytobiologica 01/2008; 46(2):143-6. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is claimed that novel beta-adrenolytic drugs possess superior antioxidant properties as compared to classical selective or non-selective beta-adrenoceptor antagonists. Here we tested this notion by analyzing radical scavenging properties of selected beta-adrenolytic drugs and their ability to release nitric oxide in biological preparations. Selective beta1-adrenolytics such as nebivolol, atenolol, metoprolol and non-selective beta-adrenolytics with alpha1-receptor blocking properties such as carvedilol and labetalol were chosen for analysis. NO-releasing properties of nebivolol and carvedilol distinguished third generation beta-adrenolytics from their older counterparts while the reactivity towards hydroxyl and peroxyl radicals discerns only carvedilol but not nebivolol. Thus, superior clinical efficacy of third generation beta-adrenolytics may be related to their ability to release NO rather then to their direct antioxidant properties.
Free Radical Research 08/2006; 40(7):741-52. · 3.28 Impact Factor