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L -arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME- induced hypertension
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ABSTRACTS / Journal of Molecular and Cellular Cardiology 44 (2008) 711–825
Matthias Karck, Gábor Szabó. Department of Cardiac Surgery, University of Heidelberg, Germany ⁎ Corresponding author. Department of Cardiac Surgery, University of Heidelberg, INF 326. OG. 2, 69120 Heidelberg, Germany. Tel.: +49 6221 566246; fax: +49 6221 564571. E-mail address: [email protected] Overproduction of free radicals in aging tissues causes nitrooxidative stress and molecular inflammatory reactions, which play an important role in the pathogenesis of cardiovascular dysfunction associated with aging. It has been reported, that the copper(II) aspirinate complex (CuAsp) exerts not only the anti-inflammatory and platelet anti-aggregating effects of aspirin, but due to its superoxide dismutase mimetic activity, it acts as an antioxidant as well. In this study we investigated the effects of CuAsp on agingassociated cardiovascular dysfunction. Aging (24 months) and young (3 months) rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg/day). Left ventricular pressure–volume (PV) relations were measured by using a microtip Millar PV conductance catheter, and indexes of contractility (e.g. slope of ESPVR (Emax)) were calculated. In organ bath experiments for isometric tension endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine (ACh) and sodium nitroprusside (SNP). When compared to the young controls, aging rats showed impaired left ventricular contractility (Emax: 0.51 ± 0.04 vs. 2.16 ± 0.28 mm Hg/ μl; p b 0.05) and a marked endothelial dysfunction (max. relaxation to ACh: 66.66 ± 1.30 vs. 87.09± 1.35%; p b 0.05). Treatment with CuAsp resulted in a significantly improved cardiac function (Emax: 1.21 ± 0.17 vs. 0.51± 0.04 mm Hg/μl) and higher vasorelaxation to ACh in aging rats (94.83 ± 0.73 vs. 66.66± 1.30%). The treatment did not influence the cardiovascular functions of young rats. Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp. Keywords: Aging; Cardiovascular dysfunction; Copper(II) aspirinate
Republic. Tel.: +421 2 59357276; fax: +421 2 59357601. E-mail address: [email protected] Aim: NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Methods: Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), and control 7 (7 weeks placebo). Results: L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic, contractile and soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison to the control group. Conclusion: The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone. VEGA grant 1/3429/06 and 2/6148/26. Keywords: L-arginine; Spironolactone; L-NAME-hypertension doi:10.1016/j.yjmcc.2008.02.241
doi:10.1016/j.yjmcc.2008.02.240
Abstract No. 241 Abstract No. 240 L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension F. Simko a,⁎, A. Potacova b, V. Pelouch c, L. Paulis a,d, J. Matuskova a, K. Krajcirovicova a, O. Pechanova d, M. Adamcova b. a Department of Pathophysiology, School of Medicine, Comenius University, Slovak Republic. b Department of Physiology, School of Medicine, Hradec Králové, Czech Republic. c Department of Medical Chemistry, 2nd School of Medicine, Prague, Czech Republic. d Instit. Physiol., SAS, Bratislava, Slovak Republic ⁎ Corresponding author. Department of Pathophysiology, School of Medicine, Komensky University, 81372 Bratislava, Slovak
Comparison of melatonin, captopril and simvastatin on the heart remodeling in spontaneously hypertensive rats F. Simko a,⁎, L. Paulis a,b, A. Potacova c, V. Pelouch d, K. Krajcirovicova a, S. Kojsova, Z. Csizmadiova, M. Adamcova c, O. Pechanova. a Department of Pathophysiology, School of Medicine, Comenius University, Slovak Republic. b Department of Physiology, School of Medicine, Hradec Králové, Czech Republic. c Department of Medicinal Chemistry and Biochemistry, 2nd School of Medicine, Prague, Czech Republic. d Institute of Physiology, Slovak Academy of Science, Bratislava, Slovak Republic ⁎ Corresponding author. Department of Pathophysiology, School of Medicine, Komensky University, Sasinkova 4, 813 72 Bratislava, Slovak Republic. Tel.: +421 259357276; fax: +421 259357601. E-mail address: [email protected]
ABSTRACTS / Journal of Molecular and Cellular Cardiology 44 (2008) 711–825
Matthias Karck, Gábor Szabó. Department of Cardiac Surgery, University of Heidelberg, Germany ⁎ Corresponding author. Department of Cardiac Surgery, University of Heidelberg, INF 326. OG. 2, 69120 Heidelberg, Germany. Tel.: +49 6221 566246; fax: +49 6221 564571. E-mail address: [email protected] Overproduction of free radicals in aging tissues causes nitrooxidative stress and molecular inflammatory reactions, which play an important role in the pathogenesis of cardiovascular dysfunction associated with aging. It has been reported, that the copper(II) aspirinate complex (CuAsp) exerts not only the anti-inflammatory and platelet anti-aggregating effects of aspirin, but due to its superoxide dismutase mimetic activity, it acts as an antioxidant as well. In this study we investigated the effects of CuAsp on agingassociated cardiovascular dysfunction. Aging (24 months) and young (3 months) rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg/day). Left ventricular pressure–volume (PV) relations were measured by using a microtip Millar PV conductance catheter, and indexes of contractility (e.g. slope of ESPVR (Emax)) were calculated. In organ bath experiments for isometric tension endothelium-dependent and -independent vasorelaxation of isolated aortic rings were investigated by using acetylcholine (ACh) and sodium nitroprusside (SNP). When compared to the young controls, aging rats showed impaired left ventricular contractility (Emax: 0.51 ± 0.04 vs. 2.16 ± 0.28 mm Hg/ μl; p b 0.05) and a marked endothelial dysfunction (max. relaxation to ACh: 66.66 ± 1.30 vs. 87.09± 1.35%; p b 0.05). Treatment with CuAsp resulted in a significantly improved cardiac function (Emax: 1.21 ± 0.17 vs. 0.51± 0.04 mm Hg/μl) and higher vasorelaxation to ACh in aging rats (94.83 ± 0.73 vs. 66.66± 1.30%). The treatment did not influence the cardiovascular functions of young rats. Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp. Keywords: Aging; Cardiovascular dysfunction; Copper(II) aspirinate
Republic. Tel.: +421 2 59357276; fax: +421 2 59357601. E-mail address: [email protected] Aim: NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Methods: Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), and control 7 (7 weeks placebo). Results: L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic, contractile and soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison to the control group. Conclusion: The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone. VEGA grant 1/3429/06 and 2/6148/26. Keywords: L-arginine; Spironolactone; L-NAME-hypertension doi:10.1016/j.yjmcc.2008.02.241
doi:10.1016/j.yjmcc.2008.02.240
Abstract No. 241 Abstract No. 240 L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension F. Simko a,⁎, A. Potacova b, V. Pelouch c, L. Paulis a,d, J. Matuskova a, K. Krajcirovicova a, O. Pechanova d, M. Adamcova b. a Department of Pathophysiology, School of Medicine, Comenius University, Slovak Republic. b Department of Physiology, School of Medicine, Hradec Králové, Czech Republic. c Department of Medical Chemistry, 2nd School of Medicine, Prague, Czech Republic. d Instit. Physiol., SAS, Bratislava, Slovak Republic ⁎ Corresponding author. Department of Pathophysiology, School of Medicine, Komensky University, 81372 Bratislava, Slovak
Comparison of melatonin, captopril and simvastatin on the heart remodeling in spontaneously hypertensive rats F. Simko a,⁎, L. Paulis a,b, A. Potacova c, V. Pelouch d, K. Krajcirovicova a, S. Kojsova, Z. Csizmadiova, M. Adamcova c, O. Pechanova. a Department of Pathophysiology, School of Medicine, Comenius University, Slovak Republic. b Department of Physiology, School of Medicine, Hradec Králové, Czech Republic. c Department of Medicinal Chemistry and Biochemistry, 2nd School of Medicine, Prague, Czech Republic. d Institute of Physiology, Slovak Academy of Science, Bratislava, Slovak Republic ⁎ Corresponding author. Department of Pathophysiology, School of Medicine, Komensky University, Sasinkova 4, 813 72 Bratislava, Slovak Republic. Tel.: +421 259357276; fax: +421 259357601. E-mail address: [email protected]