There is ample evidence on the benefit of angiotensin receptor-neprilysin inhibitors (ARNIs) in heart failure, yet data regarding the potential protective action of ARNIs in hypertensive heart disease are sparse. The aim of this study was to show whether an ARNI exerts a protective effect in a model of Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension with a hypertensive heart and to compare this potential benefit with an angiotensin-converting enzyme inhibitor, captopril. Five groups of adult male Wistar rats were studied (14 per group) for four weeks: untreated controls; ARNI (68 mg/kg/day); L-NAME (40 mg/kg/day); L-NAME treated with ARNI; and L-NAME treated with captopril (100 mg/kg/day). L-NAME administration induced hypertension, accompanied by increased left ventricular (LV) weight and fibrotic rebuilding of the LV in terms of increased concentration and content of hydroxyproline in insoluble collagen and in total collagen and with a histological finding of fibrosis. These alterations were associated with a compromised systolic and diastolic LV function. Treatment with either an ARNI or captopril reduced systolic blood pressure (SBP), alleviated LV hypertrophy and fibrosis, and prevented the development of both systolic and diastolic LV dysfunction. Moreover, the serum levels of prolactin and prolactin receptor were reduced significantly by ARNI and slightly by captopril. In conclusion, in L-NAME-induced hypertension, the dual inhibition of neprilysin and AT1 receptors by ARNI reduced SBP and prevented the development of LV hypertrophy, fibrosis, and systolic and diastolic dysfunction. These data suggest that ARNI could provide protection against LV structural remodeling and functional disorders in hypertensive heart disease.
- Publikační typ
- časopisecké články MeSH
This study investigated whether sacubitril/valsartan or valsartan are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in two experimental models of pre-hypertension induced by continuous light (24 hours/day) exposure or by chronic lactacystin treatment, and how this potential protection interferes with the renin-angiotensin-aldosterone system (RAAS). Nine groups of three-month-old male Wistar rats were treated for six weeks as follows: untreated controls (C), sacubitril/valsartan (ARNI), valsartan (Val), continuous light (24), continuous light plus sacubitril/valsartan (24+ARNI) or valsartan (24+Val), lactacystin (Lact), lactacystin plus sacubitil/valsartan (Lact+ARNI) or plus valsartan (Lact+Val). Both the 24 and Lact groups developed a mild but significant systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, as well as LV systolic and diastolic dysfunction. Yet, no changes in serum renin-angiotensin were observed either in the 24 or Lact groups, though aldosterone was increased in the Lact group compared to the controls. In both models, sacubitril/valsartan and valsartan reduced elevated SBP, LV hypertrophy and fibrosis and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan and valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7 in the 24 and Lact groups and reduced aldosterone in the Lact group. We conclude that both continuous light exposure and lactacystin treatment induced normal-to-low serum renin-angiotensin models of pre-hypertension, whereas aldosterone was increased in lactacystin-induced pre-hypertension. The protection by ARNI or valsartan in the hypertensive heart in either model was related to the Ang II blockade and the protective Ang 1-7, while in lactacystin-induced pre-hypertension this protection seems to be additionally related to the reduced aldosterone level.
- MeSH
- acetylcystein analogy a deriváty MeSH
- aldosteron MeSH
- aminobutyráty * MeSH
- bifenylové sloučeniny farmakologie MeSH
- fibróza MeSH
- fixní kombinace léků MeSH
- hypertenze * farmakoterapie MeSH
- hypertrofie levé komory srdeční MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- prehypertenze * MeSH
- renin-angiotensin systém MeSH
- renin MeSH
- srdeční selhání * MeSH
- tepový objem MeSH
- tetrazoly farmakologie terapeutické užití MeSH
- valsartan farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Lactacystin is a specific proteasome inhibitor that blocks the hydrolysis of intracellular proteins by ubiquitin/proteasome system inhibition. The administration of lactacystin to rats induced hypertension and remodeling of the left ventricle and aorta. This study tested whether lactacystin induces structural and fibrotic rebuilding of the kidneys and whether melatonin and captopril can prevent these potential changes. Six weeks of lactacystin administration to rats increased their average systolic blood pressure (SBP). In the kidneys, lactacystin reduced glomerular density, increased the glomerular tuft area, and enhanced hydroxyproline concentrations. It also elevated the intraglomerular proportion including the amounts of collagen (Col) I and Col III. Lactacystin also raised the tubulointerstitial amounts of Col I and the sum of Col I and Col III with no effect on vascular/perivascular collagen. Six weeks of captopril treatment reduced SBP, while melatonin had no effect. Both melatonin and captopril increased glomerular density, reduced the glomerular tuft area, and lowered the hydroxyproline concentration in the kidneys. Both drugs reduced the proportion and total amounts of intraglomerular and tubulointerstitial Col I and Col III. We conclude that chronic lactacystin treatment stimulated structural and fibrotic remodeling of the kidneys, and melatonin and captopril partly prevented these alterations. Considering the effect of lactacystin on both the heart and kidneys, chronic treatment with this drug may be a prospective model of cardiorenal damage suitable for testing pharmacological drugs as protective agents.
- Publikační typ
- časopisecké články MeSH
Laterálna epikondylitída (LE – lateral epicondylitis) je častým problémom u pacientov vyššieho veku, ale tiež u športovcov. LE sa zaraďuje medzi najčastejšie príčiny bolesti lakťa u dospelých, tiež je častým problémom u zamestnaní s chronickým preťažovaním daného segmentu. Medzi typické symptómy sa zaraďuje bolesť v oblasti laterálnej časti lakťa. Táto bolesť môže vyžarovať smerom do predlaktia. Priebeh LE môže byť akútny, ale aj chronický. Etiológia nebola presne identifikovaná. V rámci klinického vyšetrenia je možné využiť viacero diagnostických manévrov ako Mill test, Cozen test, Maudsley test a Polk test. Pri liečbe sa používa viacero terapeutických modalít. Najčastejšie sa pri liečbe LE používa cvičenie. Medzi základne typy cvičenia pri jej liečbe patrí izometrické, koncentrické a najčastejšie používané excentrické cvičenie. Pri liečbe LE sú používané aj ďalšie terapeutické modality ako kineziotejp, manuálna terapia a rôzne formy fyzikálnej terapie.
Lateral epicondylitis (LE) is a painful condition that affects mainly older patients, but also athletes. Also known as tennis elbow, it belongs to most common causes of elbow pain in adults and is among the most frequent disorders caused by overuse. Typical symptoms include pain located in the lateral part of the elbow likely to radiate to the forearm. The process of lateral epicondylitis can be both acute and chronic. The aetiology of LE has not been exactly determined yet. Within clinical examination, it is possible to use several diagnostic tests such as Mill test, Cozen test, Maudsley test and Polk test. The treatment methods include various therapeutic modalities. The most common method of LE treatment is exercise. The basic types of exercise include isometric and concentric exercises; however, the most commonly used are eccentric exercises. Other therapeutic approaches consist of kinesio taping, manual therapy, and various types of physical therapy.
- MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- myalgie etiologie patologie terapie MeSH
- rehabilitace metody MeSH
- techniky cvičení a pohybu MeSH
- tejpovací páska MeSH
- tenisový loket * diagnóza patologie rehabilitace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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.
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- funkce levé komory srdeční účinky léků MeSH
- infarkt myokardu patofyziologie MeSH
- isoprenalin MeSH
- ivabradin aplikace a dávkování farmakologie MeSH
- kardiotonika aplikace a dávkování farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- remodelace komor účinky léků MeSH
- srdeční selhání farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Džudo patrí medzi bojové umenia rozšírené po celom svete. Významnú problematiku predstavujú zranenia dolných končatín u džudistov. Dôležitú úlohu v prevencii zranení zohráva optimálna dynamická stabilita. Pre vysoké riziko zranenia dolných končatín sme sa rozhodli otestovať dynamickú stabilitu u profesionálnych džudistov Vojenského športového centra DUKLA Banská Bystrica.Metóda: Y Balance Test (YBT) je pomôcka, ktorá sa používa ako test na meranie dynamickej stability a určenie potenciálneho rizika zranenia dolnej končatiny. YBT vyžaduje pri meraní dolných končatín u športovca udržiavanie rovnováhy, sily, koordinácie a stability na jednej nohe so súčasným posunom druhej nohy po mernej podložke v tvare písmena Y čo najďalej, a to v troch rôznych smeroch - anteriórne, posterolaterálne a posteromediálne.Výsledky: Priemerná hodnota YBT kompozitného skóre u džudistov bola 102,6 (SD± 10,28) a 103,26 (SD± 8,33) na ľavej, resp. pravej dolnej končatine. Priemerná hodnota YBT kompozitného skóre v kontrolnej skupine bola 106,76 (SD± 7,20) a 106,88 (SD± 8,30) na ľavej, resp. pravej dolnej končatine. Rozdiel medzi kompozitným skóre ľavej dolnej končatiny u oboch skupín a pravej dolnej končatiny u oboch sledovaných skupín nebol štatisticky signifikantný (p<0,05).Záver: Výsledky Y Balance testu neboli lepšie u džudistov v porovnaní s kontrolnou vrcholovo nešportujúcou populáciou.
Introduction: Judo is one of the most common martial arts around the world. Lower limb injuries in judo are a significant issue. Optimal dynamic stability plays an important role in injury prevention. Due to the high risk of injury to the lower limbs, we decided to test the dynamic stability of professional judokas of the Military Sports Center DUKLA Banská Bystrica.Method: The Y Balance Test (YBT) is a device used as a test to measure dynamic stability and determine the potential risk of lower limb injury. When measuring the athlete's lower limbs, YBT requires maintaining balance, strength, coordination and stability on one leg while moving the other leg along the Y-shaped measuring pad as far as possible, in three different directions, anterior, posterolateral and posteromedial.Results: The mean value of the YBT composite score in judoists was 102.6 (SD ± 10.28) and 103.26 (SD ± 8.33) on the left and left, respectively. right lower limb. The mean YBT composite score in the control group was 106.76 (SD ± 7.20) and 106.88 (SD ± 8.30) on the left, respectively. right lower limb. The difference between the composite score of the left lower limb in both groups and the right lower limb in both groups was not statistically significant (p <0.05).Conclusion: The results of the Y Balance Test were not better in professional judoists compared to the control non-sporting population.
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 If 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.
- Publikační typ
- časopisecké články MeSH
There is a great urgency of detecting and monitoring myocardial fibrosis in clinical practice with the aim to improve and personalize therapy against cardiac remodelling. Hence, the aim of this study was to describe alterations in and show potential correlations between the structural characteristics and the molecular and biochemical markers of cardiac remodelling on a model of isoproterenol-induced heart failure. Two groups of 3-month-old male Wistar rats (n = 8 per group) were sacrificed after four weeks of treatment: control (placebo), ISO (5 mg/kg/day intraperitoneally). Chronic ISO treatment led to heart failure (HF) characterized by significant reduction of systolic blood pressure (SBP) accompanied by an increase in left ventricular weight (LVW) along with increased collagen content in the LV. The collagen content correlated negatively with SBP (R = -0.776, P < 0.001) and positively with LVW (R = 0.796, P < 0.001), with Col1a1 (0.83; P < 0.001) and Acta2 (0.73; P < 0.01). Moreover, the mRNA expression of fibrotic remodelling indicator, i.e. TGF-β1 tended to increase, while the level of fibrinolysis markers (MCP-1, TIMP-2, MMP) were unchanged. The plasma markers of collagen, procollagen I C-terminal propeptide (PICP) was 37.34 ± 7.10 pg/mL in control and was reduced by 42% (P < 0.05) in the ISO group and procollagen III N-terminal propeptide (PIIINP) was 1216.7 ± 191.0 pg/mL in control and was decreased by 66% (P < 0.05) in the ISO group. Surprisingly, there was no positive correlation between plasma markers of collagen, i.e. PICP and PIIINP and collagen content or molecular markers of collagen. However, both PICP and PIIINP correlated with BW (R = 0.712, resp. 0.803, P < 0.001), which was significantly reduced (by 25%, P < 0.05) in the ISO group. In conclusion, we assume that the collagen content of the left ventricle does not need unavoidably correlate with plasma markers of collagen, which might be affected by confounding factors in heart failure, such as loss of body weight, presumably associated with a catabolic condition.
- MeSH
- isoprenalin MeSH
- kolagen metabolismus MeSH
- krevní tlak MeSH
- peptidové fragmenty krev MeSH
- potkani Wistar MeSH
- prokolagen krev MeSH
- remodelace komor * MeSH
- srdeční komory metabolismus MeSH
- srdeční selhání chemicky indukované metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
