146 results on '"Paulis, Ludovit"'
Search Results
2. Melatonin as a rational alternative in the conservative treatment of resistant hypertension
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Simko, Fedor, Reiter, Russel J., and Paulis, Ludovit
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- 2019
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3. 17[beta]-Estradiol treatment reversed left ventricular dysfunction in castrated male rats: an echocardiographic study
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Baka, Tomas, Hodosy, Julius, Krajcirovicova, Kristina, Repova, Kristina, Aziriova, Silvia, Domonkos, Emese, Borbelyova, Veronika, Slavkovsky, Peter, Zorad, Stefan, Celec, Peter, Paulis, Ludovit, and Simko, Fedor
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Care and treatment ,Usage ,Health aspects ,Estradiol -- Usage -- Health aspects ,Heart diseases -- Care and treatment ,Left heart ventricle -- Care and treatment - Abstract
Introduction Left ventricular hypertrophy and heart failure are crucial problems in nowadays cardiology (Simko et al. 2014). Sex-based differences regarding heart function and outcomes were observed in various cardiovascular pathologies [...], No data are available on heart function in chronic testosterone deficiency and on the effect of estrogen treatment. Eighteen 4-week-old male Lewis rats were randomly divided into 3 groups (n = 6): 1 group of sham-operated rats and 2 groups of castrated rats. Sixty-six weeks after surgery, 1 castrated group received a dose of 17[beta]-estradiol (10 [micro]g/kg per day) and the remaining 2 groups received a placebo subcutaneously for 14 days. Left ventricular (LV) systolic and diastolic functions were measured by transthoracic echocardiography. Castration decreased LV ejection fraction (9%) and fractional shortening (15%) and deteriorated LV diastolic function (94%). 17[beta]3-Estradiol treatment increased LV ejection fraction (15%) and fractional shortening (31%) and improved LV diastolic function (48%). Plasma testosterone concentrations were decreased in both castrated groups. In conclusion, chronic testosterone deficiency induced LV systolic and diastolic dysfunction; these disorders were reversed by short-term treatment with 17[beta]-estradiol. Keywords: chronic testosterone deficiency, 17[beta]3-estradiol, systolic dysfunction, diastolic dysfunction, echocardiography. Aucune donnee n'est accessible quant a la fonction cardiaque en cas de carence prolongee en testosterone ni sur l'effet de l'restrogenotherapie. Nous avons reparti aleatoirement 18 rats Lewis males de 4 semaines dans trois groupes (n = 6): un groupe avec intervention chirurgicale factice (sham) et deux groupes de rats castres. Soixante-six semaines apres l'intervention chirurgicale, l'un des groupes de rats castres a recu une dose de 17[beta]3-estradiol (10 [micro]g/kg par jour) et les deux autres groupes ont recu un placebo, dans les trois cas par voie sous-cutanee pendant 14 jours. Nous avons mesure les fonctions systolique et diastolique du ventricule gauche (VG) a l'aide de l'echocardiographie transthoracique. La castration a entraine une diminution de la fraction d'ejection du VG (9%) avec un raccourcissement fractionnel (15%) et une deterioration de la fonction diastolique du VG (94%). L'administration de 17[beta]3-estradiol a entraine une augmentation de la fraction d'ejection du VG (15%) avec un raccourcissement fractionnel (31%) et une amelioration de la fonction diastolique du VG (48%). Les concentrations plasmatiques de testosterone s'abaissaient dans les deux groupes de rats castres. En conclusion, la carence prolongee en testosterone entrainait un dysfonctionnement systolique et diastolique du ventricule gauche; ces troubles s'inversaient avec l'administration de 17[beta]3-estradiol a court terme. [Traduit par la Redaction] Mots-cles : carence prolongee en testosterone, 17[beta]3-estradiol, dysfonctionnement systolique, dysfonctionnement diastolique, echocardiographie.
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- 2018
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4. AT2-receptor stimulation enhances axonal plasticity after spinal cord injury by upregulating BDNF expression
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Namsolleck, Pawel, Boato, Francesco, Schwengel, Katja, Paulis, Ludovit, Matho, Katherine S., Geurts, Nathalie, Thöne-Reineke, Christa, Lucht, Kristin, Seidel, Kerstin, Hallberg, Anders, Dahlöf, Björn, Unger, Thomas, Hendrix, Sven, and Steckelings, U. Muscha
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- 2013
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5. Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders
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Paulis, Ludovit, Foulquier, Sébastien, Namsolleck, Pawel, Recarti, Chiara, Steckelings, Ulrike Muscha, and Unger, Thomas
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- 2016
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6. New Developments in the Pharmacological Treatment of Hypertension: Dead-End or a Glimmer at the Horizon?
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Paulis, Ludovit, Rajkovicova, Romana, and Simko, Fedor
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- 2015
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7. Cannabinoid receptor 1 inhibition improves cardiac function and remodelling after myocardial infarction and in experimental metabolic syndrome
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Slavic, Svetlana, Lauer, Dilyara, Sommerfeld, Manuela, Kemnitz, Ulrich Rudolf, Grzesiak, Aleksandra, Trappiel, Manuela, Thöne-Reineke, Christa, Baulmann, Johannes, Paulis, Ludovit, Kappert, Kai, Kintscher, Ulrich, Unger, Thomas, and Kaschina, Elena
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- 2013
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8. Monocrotaline-Induced Pulmonary Arterial Hypertension and Bosentan Treatment in Rats: Focus on Plasma and Erythrocyte Parameters.
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Jasenovec, Tomas, Radosinska, Dominika, Kollarova, Marta, Vrbjar, Norbert, Balis, Peter, Trubacova, Simona, Paulis, Ludovit, Tothova, Lubomira, Shawkatova, Ivana, and Radosinska, Jana
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PULMONARY arterial hypertension ,ERYTHROCYTES ,ERYTHROCYTE deformability ,PLASMA focus ,RENIN-angiotensin system ,VASCULAR smooth muscle ,MATRIX metalloproteinases ,ANGIOTENSIN II - Abstract
The objective of our study was to contribute to the characterization of monocrotaline-induced pulmonary arterial hypertension (PAH) in a rat model, with emphasis on the renin–angiotensin–aldosterone system, parameters of oxidative stress, the activity of matrix metalloproteinases, and erythrocyte parameters. Moreover, we aimed to analyze the effects of bosentan. Experiments were performed on 12-week-old male Wistar rats randomly assigned to 3 groups: control, monocrotaline-treated (60 mg/kg), and monocrotaline combined with bosentan (300 mg/kg/day). Our study confirmed the well-known effects of monocrotaline administration on lungs and the right ventricle, as well as pulmonary arterial pressure. In addition, we observed activation of the alternative pathway of the renin–angiotensin system, namely an increase in angiotensin (Ang) 1–7 and Ang 1-5 together with an increase in Ang I, but without any change in Ang II level, and downregulation of aldosterone 4 weeks after monocrotaline administration. For the first time, modifications of erythrocyte Na,K-ATPase enzyme kinetics were demonstrated as well. Our observations do not support data obtained in PAH patients showing an increase in Ang II levels, increase in oxidative stress, and deterioration in RBC deformability. Although bosentan primarily targets the vascular smooth muscle, our study confirmed its antioxidant effect. The obtained data suggest that besides the known action of bosentan, it decreases heart rate and increases erythrocyte deformability, and hence could have a beneficial hemodynamic effect in the PAH condition. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Regression of L-NAME–Induced Hypertension: The Role of Nitric Oxide and Endothelium-Derived Constricting Factor
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Paulis, Ludovit, Zicha, Josef, Kunes, Jaroslav, Hojna, Silvie, Behuliak, Michal, Celec, Peter, Kojsova, Stanislava, Pechanova, Olga, and Simko, Fedor
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- 2008
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10. The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension
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Pechánová, Olga, Zicha, Josef, Paulis, Ludovít, Zenebe, Woineshet, Dobesová, Zdenka, Kojsová, Stanislava, Jendeková, Lýdia, Sládková, Martina, Dovinová, Ima, Simko, Fedor, and Kunes, Jaroslav
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- 2007
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11. Sacubitril/Valsartan and Ivabradine Attenuate Left Ventricular Remodelling and Dysfunction in Spontaneously Hypertensive Rats: Different Interactions with the Renin–Angiotensin–Aldosterone System.
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Simko, Fedor, Baka, Tomas, Stanko, Peter, Repova, Kristina, Krajcirovicova, Kristina, Aziriova, Silvia, Domenig, Oliver, Zorad, Stefan, Adamcova, Michaela, and Paulis, Ludovit
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RENIN-angiotensin system ,IVABRADINE ,ENTRESTO ,VALSARTAN ,HYPERTENSION - Abstract
This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Key advances in antihypertensive treatment
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Paulis, Ludovit, Steckelings, Ulrike M., and Unger, Thomas
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- 2012
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13. Therapeutic perspectives in hypertension: novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches
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Unger, Thomas, Paulis, Ludovit, and Sica, Domenic A.
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- 2011
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14. Novel therapeutic targets for hypertension
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Paulis, Ludovit and Unger, Thomas
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- 2010
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15. Melatonin interactions with blood pressure and vascular function during l-NAME-induced hypertension
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Paulis, Ludovit, Pechanova, Olga, Zicha, Josef, Barta, Andrej, Gardlik, Roman, Celec, Peter, Kunes, Jaroslav, and Simko, Fedor
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- 2010
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16. Chronotherapy beyond blood pressure reduction?
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Simko, Fedor and Paulis, Ludovit
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- 2008
17. Melatonin as a potential antihypertensive treatment
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Simko, Fedor and Paulis, Ludovit
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- 2007
18. Ivabradine improves survival and attenuates cardiac remodeling in isoproterenol‐induced myocardial injury.
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Simko, Fedor, Baka, Tomas, Repova, Kristina, Aziriova, Silvia, Krajcirovicova, Kristina, Paulis, Ludovit, and Adamcova, Michaela
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IVABRADINE ,MYOCARDIAL injury ,SURVIVAL rate ,SYSTOLIC blood pressure ,LABORATORY rats ,ISOPROTERENOL - Abstract
This study investigated whether ivabradine, a selective If current inhibitor reducing heart rate (HR), is able to improve survival and prevent left ventricular (LV) remodeling in isoproterenol‐induced heart damage. Wistar rats were treated for 6 weeks: controls (n = 10), ivabradine (10 mg/kg/day orally; n = 10), isoproterenol (5 mg/kg/day intraperitoneally; n = 40), and isoproterenol plus ivabradine (n = 40). Isoproterenol increased mortality, induced hypertrophy of both ventricles and LV fibrotic rebuilding, and reduced systolic blood pressure (SBP). Ivabradine significantly increased survival rate (by 120%) and prolonged average survival time (by 20%). Furthermore, ivabradine reduced LV weight and hydroxyproline content in soluble and insoluble collagen fraction, reduced HR and attenuated SBP decline. We conclude that ivabradine improved survival in isoproterenol‐damaged hearts. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Disease severity–related alterations of cardiac microRNAs in experimental pulmonary hypertension.
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Kmecova, Zuzana, Veteskova, Jana, Lelkova‐Zirova, Katarina, Bies Pivackova, Lenka, Doka, Gabriel, Malikova, Eva, Paulis, Ludovit, Krenek, Peter, and Klimas, Jan
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MICRORNA ,PULMONARY hypertension ,OXYGEN in the blood - Abstract
Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH). We hypothesized that heart‐relevant microRNAs, that is myomiRs (miR‐1, miR‐133a, miR‐208, miR‐499) and miR‐214, can have a role in the right ventricle in the development of PAH. To mimic PAH, male Wistar rats were injected with monocrotaline (MCT, 60 mg/kg, s.c.); control group received vehicle. MCT rats were divided into two groups, based on the clinical presentation: MCT group terminated 4 weeks after MCT administration and prematurely terminated group (ptMCT) displaying signs of terminal disease. Myocardial damage genes and candidate microRNAs expressions were determined by RT‐qPCR. Reduced blood oxygen saturation, breathing disturbances, RV enlargement as well as elevated levels of markers of myocardial damage confirmed PH in MCT animals and were more pronounced in ptMCT. MyomiRs (miR‐1/miR‐133a/miR‐208a/miR‐499) were decreased and the expression of miR‐214 was increased only in ptMCT group (P < 0.05). The myomiRs negatively correlated with Fulton index as a measure of RV hypertrophy in MCT group (P < 0.05), whereas miR‐214 showed a positive correlation (P < 0.05). We conclude that the expression of determined microRNAs mirrored the disease severity and targeting their pathways might represent potential future therapeutic approach in PAH. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Effects of captopril, spironolactone, and simvastatin on the cardiovascular system of non-diseased Wistar rats
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Simko, Fedor, Pechanova, Olga, Krajcirovicova, Kristina, Matuskova, Jana, Pelouch, Vaclav, Adamcova, Michaela, and Paulis, Ludovit
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- 2015
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21. Suppression of β1-Adrenoceptor Autoantibodies is Involved in the Antiarrhythmic Effects of Omega-3 Fatty Acids in Male and Female Hypertensive Rats.
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Bacova, Barbara Szeiffova, Radosinska, Jana, Wallukat, Gerd, Barancik, Miroslav, Wallukat, Anne, Knezl, Vladimir, Sykora, Matus, Paulis, Ludovit, and Tribulova, Narcis
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AUTOANTIBODIES ,OMEGA-3 fatty acids ,EICOSAPENTAENOIC acid ,DESMOGLEINS ,PROTEIN kinase C ,VENTRICULAR fibrillation ,HEART diseases ,RATS - Abstract
The arrhythmogenic potential of β1-adrenoceptor autoantibodies (β1-AA), as well as antiarrhythmic properties of omega-3 in heart diseases, have been reported while underlying mechanisms are poorly understood. We aimed to test our hypothesis that omega-3 (eicosapentaenoic acid-EPA, docosahexaenoic acid-DHA) may inhibit matrix metalloproteinase (MMP-2) activity to prevent cleavage of β1-AR and formation of β1-AA resulting in attenuation of pro-arrhythmic connexin-43 (Cx43) and protein kinase C (PKC) signaling in the diseased heart. We have demonstrated that the appearance and increase of β1-AA in blood serum of male and female 12-month-old spontaneously hypertensive rats (SHR) was associated with an increase of inducible ventricular fibrillation (VF) comparing to normotensive controls. In contrast, supplementation of hypertensive rats with omega-3 for two months suppressed β1-AA levels and reduced incidence of VF. Suppression of β1-AA was accompanied by a decrease of elevated myocardial MMP-2 activity, preservation of cardiac cell membrane integrity and Cx43 topology. Moreover, omega-3 abrogated decline in expression of total Cx43 as well as its phosphorylated forms at serine 368 along with PKC-ε, while decreased pro-fibrotic PKC-δ levels in hypertensive rat heart regardless the sex. The implication of MMP-2 in the action of omega-3 was also demonstrated in cultured cardiomyocytes in which desensitization of β1-AR due to permanent activation of β1-AR with isoproterenol was prevented by MMP-2 inhibitor or EPA. Collectively, these data support the notion that omega-3 via suppression of β1-AA mechanistically controlled by MMP-2 may attenuate abnormal of Cx43 and PKC-ε signaling; thus, abolish arrhythmia substrate and protect rats with an advanced stage of hypertension from malignant arrhythmias. [ABSTRACT FROM AUTHOR]
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- 2020
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22. Lisinopril reverses behavioural alterations in spontaneously hypertensive rats.
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Repova, Kristina, Aziriova, Silvia, Kovacova, Dominika, Trubacova, Simona, Baka, Tomas, Kanska, Romana, Barta, Andrej, Stanko, Peter, Zorad, Stefan, Molcan, Lubos, Adamcova, Michaela, Paulis, Ludovit, and Simko, Fedor
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LISINOPRIL ,ACE inhibitors ,SYSTOLIC blood pressure ,ANXIETY ,LABORATORY rats - Abstract
This study investigated the effect of lisinopril (angiotensin-converting enzyme inhibitor) on potential behavioural alterations in spontaneously hypertensive rats (SHR). Three groups of 15-17-week-old rats were investigated for 2 weeks: Wistar control group, SHR group and SHR+lisinopril group. Systolic blood pressure (SBP) was normal in Wistar rats, SHR expressed hypertension and lisinopril normalized the SBP. We observed increased time spent in and increased frequency of entries to the central area of the open field in SHR, while lisinopril induced a trend to reduce the time spent in the central area of the open field and reduced the frequency of entries there. There was a positive correlation between SBP and reduced anxiety-like behaviour in normotensive rats; no correlations in the SHR or SHR+lisinopril groups were observed. We conclude that lisinopril normalized the increase in SBP and partly reversed the alterations of anxiety-like behaviour in SHR. [ABSTRACT FROM AUTHOR]
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- 2019
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23. Calcium Signaling and Contractility in Cardiac Myocyte of Wolframin Deficient Rats.
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Cagalinec, Michal, Zahradníková, Alexandra, Kováčová, Dominika, Paulis, Ludovit, Kureková, Simona, Hot'ka, Matej, Pavelková, Jana, Plaas, Mario, Novotová, Marta, and Zahradník, Ivan
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CALCIUM ,WOLFRAMITE ,ENDOPLASMIC reticulum ,CONFOCAL microscopy ,MYOCARDIUM - Abstract
Wolframin (Wfs1) is a membrane protein of the sarco/endoplasmic reticulum. Wfs1 mutations are responsible for the Wolfram syndrome, characterized by diabetic and neurological symptoms. Although Wfs1 is expressed in cardiac muscle, its role in this tissue is not clear. We have characterized the effect of invalidation of Wfs1 on calcium signaling-related processes in isolated ventricular myocytes of exon5-Wfs1 deficient rats (Wfs1
-e5/-e5 ) before the onset of overt disease. Calcium transients and contraction were measured in field-stimulated isolated myocytes using confocal microscopy with calcium indicator fluo-3 AM and sarcomere length detection. Calcium currents and their calcium release-dependent inactivation were characterized in whole-cell patch-clamp experiments. At 4 months, Wfs1-e5/-e5 animals were euglycemic, and echocardiographic examination revealed fully compensated cardiac function. In field-stimulated isolated ventricular myocytes, both the amplitude and the duration of contraction of Wfs1-e5/-e5 animals were elevated relative to control Wfs1+/+ littermates. Increased contractility of myocytes resulted largely from prolonged cytosolic calcium transients. Neither the amplitude of calcium currents nor their voltage dependence of activation differed between the two groups. Calcium currents in Wfs1-e5/-e5 myocytes showed a larger extent of inactivation by short voltage prepulses applied to selectively induce calcium release-dependent inactivation of calcium current. Neither the calcium content of the sarcoplasmic reticulum, measured by application of 20 mmol/l caffeine, nor the expression of SERCA2, determined from Western blots, differed significantly in myocytes of Wfs1-e5/-e5 animals compared to control ones. These experiments point to increased duration of calcium release in ventricular myocytes of Wfs1-e5/-e5 animals. We speculate that the lack of functional wolframin might cause changes leading to upregulation of RyR2 channels resulting in prolongation of channel openings and/or a delay in termination of calcium release. [ABSTRACT FROM AUTHOR]- Published
- 2019
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24. Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension.
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Simko, Fedor, Baka, Tomas, Krajcirovicova, Kristina, Repova, Kristina, Aziriova, Silvia, Zorad, Stefan, Poglitsch, Marko, Adamcova, Michaela, Reiter, Russel J., and Paulis, Ludovit
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CARDIOVASCULAR diseases ,NITRIC-oxide synthases ,MELATONIN ,HYPERTENSION risk factors ,LEFT heart ventricle diseases ,METABOLITES ,ALDOSTERONE - Abstract
The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by L-NAME, (NLG)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old male Wistar rats (n = 10) were treated as follows for four weeks: untreated controls, rats treated with melatonin (10 mg/kg/day), rats treated with L-NAME (40 mg/kg/day), and rats treated with L-NAME + melatonin. L-NAME administration led to hypertension and left ventricular (LV) fibrosis in terms of enhancement of soluble, insoluble and total collagen concentration and content. Melatonin reduced systolic blood pressure enhancement and lowered the concentration and content of insoluble and total collagen in the LV. The serum concentration of angiotensin (Ang) 1–8 (Ang II) and its downstream metabolites were reduced in the L-NAME group and remained unaltered by melatonin. The serum aldosterone level and its ratio to Ang II (AA2-ratio) were increased in the L-NAME group without being modified by melatonin. We conclude that L-NAME-hypertension is associated with reduced level of Ang II and its downstream metabolites and increased aldosterone concentration and AA2-ratio. Melatonin exerts its protective effect in L-NAME-induced hypertension without affecting RAAS. [ABSTRACT FROM AUTHOR]
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- 2018
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25. Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia.
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Madaric, Juraj, Valachovicova, Martina, Paulis, Ludovit, Pribojova, Jana, Mateova, Renata, Sebekova, Katarina, Postulkova, Luba, Madaricova, Terezia, Bucova, Maria, Mistrik, Martin, and Vulev, Ivan
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ARGININE ,MESENCHYMAL stem cells ,CELL migration ,VETERINARY cytology ,OXIDANT status ,THERAPEUTICS - Abstract
Background: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of stem cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived mononuclear cell (BM-MNC) therapy. Methods: Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular (n = 25) or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery. Results: At 6-month follow-up, four patients died of reasons unrelated to stem cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 μmol/L, p < 0.001), in parallel with decreased tumor necrosis factor (TNF)-α (2.22 ± 0.16 to 1.94 ± 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96 ± 3.1 to 8. 67 ± 4.2 μmol/L, p = 0.02), superoxide dismutase activity (168 ± 50 to 218 ± 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 ± 182 to 598 ± 283 μg/L, p = 0.02). The number of delivered BM-MNCs significantly correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r = -0.48) and the decrease in TNF-α concentration at 6 months (p = 0.03, r = -0.44) after cell delivery. ADMA or TNF-α improvement did not correlate with the number of applied CD34
+ cells, C-reactive protein concentration, leukocyte count, or the dose of atorvastatin. Conclusions: The therapeutic benefit of BM-MNC therapy is associated with reduced ADMA levels and oxidative stress. Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be involved in the beneficial effects of stem cell therapy. Trial registration: The study was approved and retrospectively registered by ISRCTN registry, ISRCTN16096154. Registered on 26 July 2016. [ABSTRACT FROM AUTHOR]- Published
- 2017
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26. Brain Renin-Angiotensin System: Does It Exist?
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van Thiel, Bibi S., Góes Martini, Alexandre, te Riet, Luuk, Severs, David, Uijl, Estrellita, Garrelds, Ingrid M., Leijten, Frank P. J., van der Pluijm, Ingrid, Essers, Jeroen, Qadri, Fatimunnisa, Alenina, Natalia, Bader, Michael, Paulis, Ludovit, Rajkovicova, Romana, Domenig, Oliver, Poglitsch, Marko, Jan Danser, A. H., and Danser, A H Jan
- Abstract
Because of the presence of the blood-brain barrier, brain renin-angiotensin system activity should depend on local (pro)renin synthesis. Indeed, an intracellular form of renin has been described in the brain, but whether it displays angiotensin (Ang) I-generating activity (AGA) is unknown. Here, we quantified brain (pro)renin, before and after buffer perfusion of the brain, in wild-type mice, renin knockout mice, deoxycorticosterone acetate salt-treated mice, and Ang II-infused mice. Brain regions were homogenized and incubated with excess angiotensinogen to detect AGA, before and after prorenin activation, using a renin inhibitor to correct for nonrenin-mediated AGA. Renin-dependent AGA was readily detectable in brain regions, the highest AGA being present in brain stem (>thalamus=cerebellum=striatum=midbrain>hippocampus=cortex). Brain AGA increased marginally after prorenin activation, suggesting that brain prorenin is low. Buffer perfusion reduced AGA in all brain areas by >60%. Plasma renin (per mL) was 40× to 800× higher than brain renin (per gram). Renin was undetectable in plasma and brain of renin knockout mice. Deoxycorticosterone acetate salt and Ang II suppressed plasma renin and brain renin in parallel, without upregulating brain prorenin. Finally, Ang I was undetectable in brains of spontaneously hypertensive rats, while their brain/plasma Ang II concentration ratio decreased by 80% after Ang II type 1 receptor blockade. In conclusion, brain renin levels (per gram) correspond with the amount of renin present in 1 to 20 μL of plasma. Brain renin disappears after buffer perfusion and varies in association with plasma renin. This indicates that brain renin represents trapped plasma renin. Brain Ang II represents Ang II taken up from blood rather than locally synthesized Ang II. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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27. Elevated heart rate and nondipping heart rate as potential targets for melatonin: a review.
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Simko, Fedor, Baka, Tomas, Paulis, Ludovit, and Reiter, Russel J.
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HEART beat ,PHYSIOLOGICAL effects of melatonin ,CARDIOVASCULAR diseases risk factors ,AUTONOMIC nervous system ,CORONARY disease - Abstract
Elevated heart rate is a risk factor for cardiovascular and all-cause mortalities in the general population and various cardiovascular pathologies. Insufficient heart rate decline during the night, that is, nondipping heart rate, also increases cardiovascular risk. Abnormal heart rate reflects an autonomic nervous system imbalance in terms of relative dominance of sympathetic tone. There are only a few prospective studies concerning the effect of heart rate reduction in coronary heart disease and heart failure. In hypertensive patients, retrospective analyses show no additional benefit of slowing down the heart rate by beta-blockade to blood pressure reduction. Melatonin, a secretory product of the pineal gland, has several attributes, which predict melatonin to be a promising candidate in the struggle against elevated heart rate and its consequences in the hypertensive population. First, melatonin production depends on the sympathetic stimulation of the pineal gland. On the other hand, melatonin inhibits the sympathetic system in several ways representing potentially the counter-regulatory mechanism to normalize excessive sympathetic drive. Second, administration of melatonin reduces heart rate in animals and humans. Third, the chronobiological action of melatonin may normalize the insufficient nocturnal decline of heart rate. Moreover, melatonin reduces the development of endothelial dysfunction and atherosclerosis, which are considered a crucial pathophysiological disorder of increased heart rate and pulsatile blood flow. The antihypertensive and antiremodeling action of melatonin along with its beneficial effects on lipid profile and insulin resistance may be of additional benefit. A clinical trial investigating melatonin actions in hypertensive patients with increased heart rate is warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia.
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Madaric, Juraj, Klepanec, Andrej, Valachovicova, Martina, Mistrik, Martin, Bucova, Maria, Olejarova, Ingrid, Necpal, Roman, Madaricova, Terezia, Paulis, Ludovit, and Vulev, Ivan
- Subjects
ISCHEMIA treatment ,BONE marrow cells ,REVASCULARIZATION (Surgery) ,LIMB salvage ,WOUND healing ,THERAPEUTICS - Abstract
Background: The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with "no-option" critical limb ischemia (CLI). Methods and results: Sixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular (n = 32) or intra-arterial (n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34
+ cell count (p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) (p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger (p = 0.028), had lower C-reactive protein levels (p = 0.038), and had higher transcutaneous oxygen pressure (tcpO2 ) (p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34+ cells (p = 0.046) and baseline tcpO2 (p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage (p = 0.0008). Conclusion: Patients who benefited from autologous BMC therapy for "no-option" CLI were treated with high doses of CD34+ cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy. Trial registration: The study was approved and registered by the ISRCTN registry. Trial registration: ISRCTN16096154. Registered: 26 July 2016. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
29. Angiotensin A/Alamandine/MrgD Axis: Another Clue to Understanding Cardiovascular Pathophysiology.
- Author
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Hrenak, Jaroslav, Paulis, Ludovit, and Simko, Fedor
- Subjects
- *
RENIN-angiotensin system , *CARDIOVASCULAR agents , *ANGIOTENSINS , *PATHOLOGICAL physiology , *BLOOD pressure - Abstract
The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulations and its modulation is a challenging target for the vast majority of cardioprotective strategies. However, many biological effects of these drugs cannot be explained by the known mode of action. Our comprehension of the RAS is thus far from complete. The RAS represents an ingenious system of "checks and balances". It incorporates vasoconstrictive, pro-proliferative, and pro-inflammatory compounds on one hand and molecules with opposing action on the other hand. The list of these molecules is still not definitive because new biological properties can be achieved by minor alteration of the molecular structure. The angiotensin A/alamandine-MrgD cascade associates the deleterious and protective branches of the RAS. Its identification provided a novel clue to the understanding of the RAS. Angiotensin A (Ang A) is positioned at the "crossroad" in this system since it either elicits direct vasoconstrictive and pro-proliferative actions or it is further metabolized to alamandine, triggering opposing effects. Alamandine, the central molecule of this cascade, can be generated both from the "deleterious" Ang A as well as from the "protective" angiotensin 1-7. This pathway modulates peripheral and central blood pressure regulation and cardiovascular remodeling. Further research will elucidate its interactions in cardiovascular pathophysiology and its possible therapeutic implications. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
30. PM258 The effects of compound 21 on L-NAME-induced hypertension in rats
- Author
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Paulis, Ludovit, Becker, Sophie T., Schmerler, Patrick, Slavic, Svetlana, Kaschina, Elena, Dahloef, Bjoern, Baulmann, Johannes, Unger, Thomas, and Steckelings, Muscha
- Published
- 2014
- Full Text
- View/download PDF
31. Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice.
- Author
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Valero-Esquitino, Verónica, Lucht, Kristin, Namsolleck, Pawel, Monnet-Tschudi, Florianne, Stubbe, Tobias, Lucht, Franziska, Liu, Meng, Ebner, Friederike, Brandt, Christine, Danyel, Leon A., Villela, Daniel C., Paulis, Ludovit, Thoene-Reineke, Christa, Dahlö, Björn, Hallberg, Anders, Unger, Thomas, Sumners, Colin, and Steckelings, U. Muscha
- Subjects
ANGIOTENSIN receptors ,ENCEPHALOMYELITIS ,ANGIOTENSIN II ,T cells ,MICROGLIA ,DEMYELINATION ,LABORATORY mice ,PREVENTION - Abstract
In the present study, we evaluated stimulation of the angiotensin type 2 receptor (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel therapeutic concept for the treatment of multiple sclerosis using the model of experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21 (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell composition were estimated by immunostaining and FACS analyses of lumbar spinal cords. The in vivo study was complemented by experiments in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4
+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction in EAE-induced demyelinated areas in lumbar spinal cord tissue after AT2 R stimulation. C21-treated mice had a significantly better neurological score than vehicle-treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ ), AT2 R stimulation prevented demyelination, accelerated re-myelination and reduced the number of microglia. Cytokine synthesis and nitric oxide production by microglia in vitro were significantly reduced after C21 treatment. These results suggest that AT2 R stimulation protects the myelin sheaths in autoimmune central nervous system inflammation by inhibiting the T-cell response and microglia activation. Our findings identify the AT2 R as a potential new pharmacological target for demyelinating diseases such as multiple sclerosis. [ABSTRACT FROM AUTHOR]- Published
- 2015
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- View/download PDF
32. Peripheral and Central Effects of Melatonin on Blood Pressure Regulation.
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Pechanov, Olga, Paulis, Ludovit, and Simko, Fedor
- Subjects
- *
REGULATION of blood pressure , *MELATONIN , *ANTIHYPERTENSIVE agents , *GENE expression , *ANTIOXIDANTS , *CENTRAL nervous system diseases , *PREVENTION , *THERAPEUTICS - Abstract
The pineal hormone, melatonin (#-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-protein coupled receptors. The pleiotropic receptor-independent effects of melatonin with a possible impact on blood pressure involve the reactive oxygen species (ROS) scavenging nature, activation and over-expression of several antioxidant enzymes or their protection from oxidative damage and the ability to increase the efficiency of the mitochondrial electron transport chain. Besides the interaction with the vascular system, this indolamine may exert part of its antihypertensive action through its interaction with the central nervous system (CNS). The imbalance between the sympathetic and parasympathetic vegetative system is an important pathophysiological disorder and therapeutic target in hypertension. Melatonin is protective in CNS on several different levels: It reduces free radical burden, improves endothelial dysfunction, reduces inflammation and shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. The increased level of serum melatonin observed in some types of hypertension may be a counter-regulatory adaptive mechanism against the sympathetic overstimulation. Since melatonin acts favorably on different levels of hypertension, including organ protection and with minimal side effects, it could become regularly involved in the struggle against this widespread cardiovascular pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
33. Antifibrotic effect of melatonin—Perspective protection in hypertensive heart disease
- Author
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Simko, Fedor and Paulis, Ludovit
- Published
- 2013
- Full Text
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34. Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin.
- Author
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Simko, Fedor, Pechanova, Olga, Bednarova, Kristina Repova, Krajcirovicova, Kristina, Celec, Peter, Kamodyova, Natalia, Zorad, Stefan, Kucharska, Jarmila, Gvozdjakova, Anna, Adamcova, Michaela, and Paulis, Ludovit
- Subjects
HYPERTENSION ,CARDIOVASCULAR diseases ,LABORATORY rats ,HEART beat ,ENZYME inhibitors ,CAPTOPRIL - Abstract
Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old maleWistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100mg/kg/day) or melatonin (10mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LVhypertrophy development and onlymelatonin reduced LVhydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
35. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure.
- Author
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Danyel, Leon A., Schmerler, Patrick, Paulis, Ludovit, Unger, Thomas, and Muscha Steckelings, U.
- Subjects
ANGIOTENSIN II ,ANGIOTENSIN receptors ,FIBROSIS ,VASODILATION ,NATRIURESIS ,THERAPEUTICS - Abstract
The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors within the renin-angiotensin system, which mediate tissue-protective actions such as anti-inflammation, antifibrosis, and antiapoptosis. In recent years, several programs have been launched in order to develop drugs that act as agonists on the AT2R or MAS to take therapeutic advantage of the protective and regenerative properties of these receptors. This review article will focus on recent data obtained in preclinical animal and in vitro models with new AT2R-agonistic molecules (Compound 21 and β-amino acid substituted angiotensin II) and with relevance for blood pressure (BP) regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect of AT2R stimulation on BP in vivo. Current data indicate that although AT2R stimulation causes vasodilation ex vivo and promotes natriuresis, it does not alter BP levels in vivo acutely - at least as long as there is no additional low-dose blockade of AT1R. However, AT2R stimulation alone is able to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic effect may result in modest lowering of BP. We conclude from these preclinical data that AT2R agonists are not suitable for antihypertensive monotherapy, but that this new future drug class may be beneficial in combination with established antihypertensives for the treatment of hypertension with improved protection from end-organ damage [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
36. AT2 receptor agonists: hypertension and beyond.
- Author
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Steckelings, Ulrike M., Paulis, Ludovit, Namsolleck, Pawel, and Unger, Thomas
- Published
- 2012
- Full Text
- View/download PDF
37. Direct Angiotensin II Type 2 Receptor Stimulation in Nω-Nitro-L-Arginine-Methyl Ester-Induced Hypertension.
- Author
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Paulis, Ludovit, Becker, Sophie T. R., Lucht, Kristin, Schwengel, Katja, Slavic, Svetlana, Kaschina, Elena, Thöne-Reineke, Christa, Dahlöf, Björn, Baulmann, Johannes, Unger, Thomas, and Steckelings, U. Muscha
- Abstract
The article presents a study on the significance of pulse wave velocity in arterial hypertension. The research concludes the N
ω Nitro-L-Ariginine-Methyl administration results to increased blood pressure. The findings indicate the use of Angiotensin II type 2 receptor averted wall thickening, modulus augmentation and reduced collagen deposition.- Published
- 2012
- Full Text
- View/download PDF
38. Direct angiotensin II type 2 receptor stimulation in Nω-nitro-L-arginine-methyl ester-induced hypertension: the effect on pulse wave velocity and aortic remodeling.
- Author
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Paulis L, Becker ST, Lucht K, Schwengel K, Slavic S, Kaschina E, Thöne-Reineke C, Dahlöf B, Baulmann J, Unger T, Steckelings UM, Paulis, Ludovit, Becker, Sophie T R, Lucht, Kristin, Schwengel, Katja, Slavic, Svetlana, Kaschina, Elena, Thöne-Reineke, Christa, Dahlöf, Björn, and Baulmann, Johannes
- Abstract
Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor. Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N(ω)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (n=65) were randomly assigned to control, L-NAME, L-NAME+compound-21, L-NAME+olmesartan, and L-NAME+olmesartan+compound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressure-lowering effect, and they seem to be NO and blood pressure independent. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
39. Automated Erythema Quantification in Radiation Therapy - a Java Based Tool.
- Author
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Putora, Paul Martin, Paulis, Ludovit, and Plasswilm, Ludwig
- Subjects
- *
ERYTHEMA , *RADIOTHERAPY , *COMMA (Punctuation) , *JAVA programming language , *DIGITAL images , *GRAPHICS processing units , *PHYSIOLOGICAL effects of radiation , *ONCOLOGY , *PATHOLOGICAL physiology - Abstract
Introduction: In radiotherapy, erythema is a common side-effect, especially during radiotherapy treatment regimes that last several weeks. The measurement of erythema might be of clinical relevance, especially when standardized interpretation is possible. Aim: The aim of this article is to present a tool that can be implemented for automatized and time efficient quantification of erythema from digital images taken during radiotherapy treatment. Method: Instead of relying on commercially available graphic editors and performing manual operations on the images within these programs we developed a java based tool that can automatically evaluate the "redness" of images. These erythema values receive a score number, are connected with the date and time the pictures were taken and are exported into a comma separated values (CSV) file. Results: The Erythema values of images could be quickly evaluated with the developed tool. With spreadsheet software the exported file could be easily manipulated to produce graphical representations of erythema rise. Conclusion: Erythema quantification from digital images can be easily performed by custom developed java tools. An automated quantification provides a method of detecting an increase in erythema that may not be visible to the naked eye. [ABSTRACT FROM AUTHOR]
- Published
- 2010
40. Melatonin interactions with blood pressure and vascular function duringl-NAME-induced hypertension.
- Author
-
Paulis, Ludovit, Pechanova, Olga, Zicha, Josef, Barta, Andrej, Gardlik, Roman, Celec, Peter, Kunes, Jaroslav, and Simko, Fedor
- Subjects
- *
MELATONIN , *BLOOD pressure , *HYPERTENSION , *FEMORAL artery , *MESENTERIC artery - Abstract
The mechanisms responsible for the antihypertensive effect of melatonin are not completely understood. To elucidate the possible role of the nitric oxide (NO) pathway in the hemodynamic actions of melatonin, the effects of this indolamine on vascular function during hypertension induced by the NO-synthase (NOS) inhibitor, Nω-nitro-l-arginine-methyl ester (l-NAME) were investigated. Four groups of male adult Wistar rats were employed: control, L-NAME (40 mg/kg), melatonin (10 mg/kg) andl-NAME + melatonin for 5 wks. Systolic and diastolic blood pressure were measured invasively in the carotid artery. Conjugated dienes concentration (an oxidative load marker), NOS RNA expression and its activity and RNA expression of cyclooxygenase-(COX)-1 and COX-2 were determined in the aorta. Acetylcholine-induced responses and their NO-mediated component were evaluated in femoral and mesenteric artery. Moreover, endothelium-derived constricting factor (EDCF)-dependent vasoconstriction and inner diameter were determined in the femoral artery. Chronicl-NAME treatment induced hypertension, elevated the oxidative load and inhibited NOS activity. Moreover, impaired NO-dependent relaxation, augmented EDCF-constriction, increased COX-2 expression and reduced arterial inner diameter were observed. Melatonin added tol-NAME treatment completely prevented elevation of the oxidative load in the aorta. However, melatonin was not able to prevent NOS activity decline, elevation of COX-2 expression or the impairment of vascular responses (except moderate improvement in relaxation of small mesenteric arteries) and it exerted only slight antihypertensive effect. In conclusion, in addition to the reduction of the oxidative load, the restoration of the NO pathway seems to play an important role in the antihypertensive effect of melatonin. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
41. Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats.
- Author
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Benova, Miroslava, Herichova, Iveta, Stebelova, Katarina, Paulis, Ludovit, Krajcirovicova, Kristina, Simko, Fedor, and Zeman, Michal
- Published
- 2009
- Full Text
- View/download PDF
42. Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19.
- Author
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Rajtik, Tomas, Galis, Peter, Bartosova, Linda, Paulis, Ludovit, Goncalvesova, Eva, and Klimas, Jan
- Subjects
COVID-19 ,ANGIOTENSIN converting enzyme ,RENIN-angiotensin system ,RESPIRATORY diseases ,ANGIOTENSIN II - Abstract
Alternative branches of the classical renin–angiotensin–aldosterone system (RAS) represent an important cascade in which angiotensin 2 (AngII) undergoes cleavage via the action of the angiotensin-converting enzyme 2 (ACE2) with subsequent production of Ang(1-7) and other related metabolites eliciting its effects via Mas receptor activation. Generally, this branch of the RAS system is described as its non-canonical alternative arm with counterbalancing actions to the classical RAS, conveying vasodilation, anti-inflammatory, anti-remodeling and anti-proliferative effects. The implication of this branch was proposed for many different diseases, ranging from acute cardiovascular conditions, through chronic respiratory diseases to cancer, nonetheless, hypoxia is one of the most prominent common factors discussed in conjugation with the changes in the activity of alternative RAS branches. The aim of this review is to bring complex insights into the mechanisms behind the various forms of hypoxic insults on the activity of alternative RAS branches based on the different duration of stimuli and causes (acute vs. intermittent vs. chronic), localization and tissue (heart vs. vessels vs. lungs) and clinical relevance of studied phenomenon (experimental vs. clinical condition). Moreover, we provide novel insights into the future strategies utilizing the alternative RAS as a diagnostic tool as well as a promising pharmacological target in serious hypoxia-associated cardiovascular and cardiopulmonary diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. The effect of melatonin on vascular function in L-NAME-induced hypertension
- Author
-
Paulis, Ludovit, Pechanova, Olga, Zicha, Josef, Gardlik, Roman, Celec, Peter, Kunes, Jaroslav, and Simko, Fedor
- Published
- 2008
- Full Text
- View/download PDF
44. LA419, a novel nitric oxide donor, prevents cardiac remodeling via the endothelial nitric oxide synthase pathway: NO donors as a means of antiremodeling.
- Author
-
Paulis, Ludovit and Simko, Fedor
- Abstract
The authors discuss a study by Gema Ruiz-Hurtado and colleagues on the effect of LA419, a new organic nitrate containing a thiol group, on left ventricular hypertrophy and fibrosis induced by aortic stenosis. According to the authors, the study directs attention from therapeutic approaches aimed at restoring the neurohumoral balance by attenuating adrenergic and renin-angiotensin-aldosterone system activation back to efforts to restore the balance by the enhancement of the nitric oxide vasodilator and antiproliferative activity.
- Published
- 2007
- Full Text
- View/download PDF
45. Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension.
- Author
-
Simko, Fedor, Baka, Tomas, Poglitsch, Marko, Repova, Kristina, Aziriova, Silvia, Krajcirovicova, Kristina, Zorad, Stefan, Adamcova, Michaela, and Paulis, Ludovit
- Subjects
HYPERTENSION ,IVABRADINE ,RENIN-angiotensin system ,GENETIC pleiotropy ,HEART function tests - Abstract
Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine's interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups (n = 10/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg/kg/day), L-NAME (40 mg/kg/day), and L-NAME plus ivabradine. L-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1–8 (Ang II), Ang 1–5, Ang 1–7, Ang 1–10, Ang 2–8, and Ang 3–8 were decreased in the L-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by L-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in L-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
46. Activation of Sonic hedgehog signaling in ventricular cardiomyocytes exerts cardioprotection against ischemia reperfusion injuries.
- Author
-
Paulis, Ludovit, Fauconnier, Jeremy, Cazorla, Olivier, Thireau, Jérome, Soleti, Raffaella, Vidal, Bastien, Ouillé, Aude, Bartholome, Marion, Bideaux, Patrice, Roubille, François, Le Guennec, Jean-Yves, Andriantsitohaina, Ramaroson, Martínez, M. Carmen, and Lacampagne, Alain
- Subjects
- *
HEDGEHOG signaling proteins , *FETAL tissues , *NEOVASCULARIZATION , *RECOMBINANT proteins , *ARRHYTHMIA , *ADENOSINE triphosphate - Abstract
Sonic hedgehog (SHH) is a conserved protein involved in embryonic tissue patterning and development. SHH signaling has been reported as a cardio-protective pathway via muscle repair-associated angiogenesis. The goal of this study was to investigate the role of SHH signaling pathway in the adult myocardium in physiological situation and after ischemia-reperfusion. We show in a rat model of ischemia-reperfusion that stimulation of SHH pathway, either by a recombinant peptide or shed membranes microparticles harboring SHH ligand, prior to reperfusion reduces both infarct size and subsequent arrhythmias by preventing ventricular repolarization abnormalities. We further demonstrate in healthy animals a reduction of QTc interval mediated by NO/cGMP pathway leading to the shortening of ventricular cardiomyocytes action potential duration due to the activation of an inward rectifying potassium current sharing pharmacological and electrophysiological properties with ATP-dependent potassium current. Besides its effect on both angiogenesis and endothelial dysfunction we demonstrate here a novel cardio-protective effect of SHH acting directly on the cardiomyocytes. This emphasizes the pleotropic effect of SHH pathway as a potential cardiac therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
47. 1029 AT2 receptor stimulation and vascular remodeling in L-NAME-induced Hypertension.
- Author
-
Paulis, Ludovit, Becker, Sophie T.R., Lucht, Kristin, Schwengel, Katja, Slavic, Svetlana, Kaschina, Elena, Dahlöf, Björn, Baulmann, Johannes, Unger, Thomas, and Steckelings, U. Muscha
- Published
- 2012
- Full Text
- View/download PDF
48. 371 THE AT2 RECEPTOR AND VASCULAR REMODELING.
- Author
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Paulis, Ludovit, Becker, Sophie T.R., Lucht, Kristin, Schwengel, Katja, Slavic, Svetlana, Kaschina, Elena, Dahlöf, Björn, Baulmann, Johannes, Unger, Thomas, and Steckelings, U. Muscha
- Published
- 2012
- Full Text
- View/download PDF
49. Renin-Angiotensin-Aldosterone System: Friend or Foe-The Matter of Balance. Insight on History, Therapeutic Implications and COVID-19 Interactions.
- Author
-
Simko F, Hrenak J, Adamcova M, and Paulis L
- Subjects
- Animals, COVID-19 therapy, Humans, SARS-CoV-2 metabolism, COVID-19 physiopathology, Renin-Angiotensin System
- Abstract
The renin-angiotensin-aldosterone system (RAAS) ranks among the most challenging puzzles in cardiovascular medicine [...].
- Published
- 2021
- Full Text
- View/download PDF
50. Ivabradine Ameliorates Kidney Fibrosis in L-NAME-Induced Hypertension.
- Author
-
Stanko P, Baka T, Repova K, Aziriova S, Krajcirovicova K, Barta A, Janega P, Adamcova M, Paulis L, and Simko F
- Abstract
Hypertension-induced renal injury is characterized by structural kidney alterations and function deterioration. Therapeutics for kidney protection are limited, thus novel renoprotectives in hypertension are being continuously sought out. Ivabradine, an inhibitor of the I
f current in the sinoatrial node reducing heart rate (HR), was shown to be of benefit in various cardiovascular pathologies. Yet, data regarding potential renoprotection by ivabradine in hypertension are sparse. Thirty-six adult male Wistar rats were divided into non-diseased controls and rats with NG -nitro-L-arginine methyl ester (L-NAME)-induced hypertension to assess ivabradine's site-specific effect on kidney fibrosis. After 4 weeks of treatment, L-NAME increased the average systolic blood pressure (SBP) (by 27%), decreased glomerular density (by 28%) and increased glomerular tuft area (by 44%). Moreover, L-NAME induced glomerular, tubulointerstitial, and vascular/perivascular fibrosis by enhancing type I collagen volume (16-, 19- and 25-fold, respectively). L-NAME also increased the glomerular type IV collagen volume and the tubular injury score (3- and 8-fold, respectively). Ivabradine decreased average SBP and HR (by 8 and 12%, respectively), increased glomerular density (by 57%) and reduced glomerular tuft area (by 30%). Importantly, ivabradine decreased type I collagen volume at all three of the investigated sites (by 33, 38, and 72%, respectively) and enhanced vascular/perivascular type III collagen volume (by 67%). Furthermore, ivabradine decreased the glomerular type IV collagen volume and the tubular injury score (by 63 and 34%, respectively). We conclude that ivabradine attenuated the alterations of glomerular density and tuft area and modified renal fibrosis in a site-specific manner in L-NAME-hypertension. It is suggested that ivabradine may be renoprotective in hypertensive kidney disease., (Copyright © 2020 Stanko, Baka, Repova, Aziriova, Krajcirovicova, Barta, Janega, Adamcova, Paulis and Simko.)- Published
- 2020
- Full Text
- View/download PDF
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