Modulation of N-methyl-D-aspartate receptors in isolated rat heart

Considering the limited data about the role of N-methyl-D-aspartate receptors (NMDA-R) in cardiovascular system and heart, the aim of the present study was to examine the effects of NMDA and DL-homocysteine thiolacotne (DL-Hcy TLHC), alone and in combinations with glycine, memantine and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance in duration of 5 minutes, followed by wash-out period in duration of 10 minutes. Using sensor in the left ventricle we registered the next parameters of myocardial function: dp/dt max, dp/dt min, systolic and diastolic left ventricular pressure, and heart rate, and coronary flow (CF) was measured flowmetrically. In the coronary venous effluent spectrophotometrically were estimated following oxidative stress biomarkers: TBARS, NO2-, O2-, and H2O2. NMDA alone did not induce any change in any observed parameter, while DL-Hcy TLHC alone, as well as combined application of NMDA and DL-Hcy TLHC with glycine, induced reduction of most cardiodynamic parameters. Memantine and ifenprodil induced reduction of cardiodynamic parameters and coronary flow, as well as some oxidative stress biomarkers.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Acute effects of nandrolone decanoate on cardiodynamic parameters in isolated rat heart

Despite worldwide use of anabolic steroids in last decades, there are still contradictory informations about their acute influence on myocardium. The aim of this study was to examine the acute effects of nandrolone decanoate (ND) on cardiodynamics and coronary flow in isolated rat heart. The hearts of male Wistar albino rats (n=48, 12 per group, age 8 weeks, body mass 180–200 g) were excised and perfused according to Langendorff technique at gradually increased coronary perfusion pressures (40–120 cmH2O). After control sets of experiments, the hearts were perfused with ND in dose of 1 μM, 10 μM and 100 μM, successively. Using sensor placed in the left ventricle, we registered: maximum and minimum rate of pressure development in the left ventricle (dp/dt max and dp/dt min), systolic and diastolic left ventricular pressure (SLVP and DLVP) and heart rate (HR). Coronary flow (CF) was measured flowmetrically. The results clearly show the depression in cardiac function caused by higher doses of ND. The highest concentration of ND (100μM) induced most deleterious impact on the myocardial function and perfusion of the heart (coronary circulation), which could be of clinical significance.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

EFFICENCY OF ATORVASTATIN AND SIMVASTATIN IN IMPROVING OF CARDIAC FUNCTION DURING THE DIFFERENT DEGREE OF HYPERHOMOCYSTEINEMIA

The aim of this study was to assess the impact of atorvastatin and simvastatin on myocardial contractility during the different degrees of hyperhomocysteinemia (HHcy) in rats. Study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. Animals were exposed to pharmacology treatment with atorvastatin in dose of 3 mg/kg per day i.p. or simvastatin in dose of 5 mg/kg per day i.p. at the same time every day, according to equivalent therapeutic doses of these statins (10 mg atorvastatin = 20 mg simvastatin). After the dietary manipulation and pharmacological treatment and confirmation of HHcy, all animals were sacrificed, hearts were isolated, and cardiac function was tested according to the Langendorff technique. Size of recovery of maximum rate of left ventricular development (dp/dtmax), minimum rate of left ventricular development (dp/dtmin), systolic left ventricular development, diastolic left ventricular development, heart rate, and coronary flow at the 40, 60, 80, 100, and 120 cmH2O coronary perfusion pressure were measured in state of physiological condition (homocysteine less than 15 μmol/L), mild HHcy, and moderate HHcy. Atorvastatin treatment significantly attenuated homocysteine-induced impairment of myocyte contractility and dominantly decreased dp/dtmax, dp/dtmin, and heart rate and induced greater changes in systolic left ventricular development compared with simvastatin. Treatment with atorvastatin seems able to revert systolic abnormalities and improve contractility during the different degrees of HHcy.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

THE EFFECTS OF SULFUR-CONTAINING COMPOUNDS ON REDOX STATUS IN HOMOCYSTEINE-TREATED RATS

There is growing interest in the activity of sulfur-containing compounds on redox balance in physiological and pathological conditions, considering that some of these compounds have not only antioxidative but also pro-oxidative activities. Aim of this study was to assess possible differences in the effects of various sulfur-containing compounds on redox balance of cardiovascular system in its physiological state and in the early onset of hyperhomocysteinemia. This experimental study divided Wistar albino rats into two groups: saline-treated (control) and DL-homocysteine-treated (experimental group). Rats from experimental group were subjected to subchronic subcutaneous administration of DL-homocysteine at dose of 0.45 μmol/g body weight twice a day for 2 weeks. At the end of this period, rats were sacrificed, and blood samples were collected to be analysed for homocysteine concentration and systemic oxidative stress. Isolated rat hearts were excised and attached to the Langendorff apparatus. To assess the effects of acute administration of L-methionine, L-cysteine, N-acetylcysteine, and sodium hydrogen sulfide, the hearts were perfused individually with each of the mentioned substances at same single dose of 0.5 mmol/l for 5 min. In collected samples of coronary venous effluent oxidative stress biomarkers were determined using spectrophotometry. Total homocysteine level was significantly higher in the experimental group than in the control group, and the effects of applied sulfur-containing compounds were significantly different in experimental and control groups. DL-homocysteine induced considerable changes in functioning of cardiovascular system even before an increase in plasma homocysteine values, and action of sulfur-containing compounds varied depending on the presence of homocysteine

MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of progressive chronic kidney disease that may lead to end-stage renal disease and renal replacement therapy in childhood. Altered expression or activity of matrix metalloproteinases (MMPs) have been found in CAKUT. The MMP-1, -3, and -8 polymorphisms studied here are located in the gene promoters and alter expression. Our aim was to investigate associations of MMP polymorphisms, solely and in haplotypes, with CAKUT in children. A case-control study with 101 pediatric patients and 281 controls was performed. The MMP-1 (-1607 1G/2G), -3 (5A/6A), and -8 (-799 C/T) genotypes were determined by PCR-restriction fragment length polymorphism. We found statistically significant associations of MMP-3 5A/6A polymorphism (p LT 0.0001) and 1G(-1607)-6A haplotype, with no preferences for MMP-8 -799C or T alleles, with CAKUT (OR = 2.93, 95 % CI 1.43-5.98, adjusted for gender, p = 0.003) and with obstructive uropathies in a subgroup of patients (OR = 4.57, 95 % CI 2.74-7.61, adjusted for gender, p LT 0.0001). MMP-3 genotypes and MMP-3 and -1 haplotypes encompassing either MMP-8 -799C or T alleles were associated with CAKUT and obstructive uropathies in pediatric patients. Still, functional and association studies are needed to elucidate evident roles of MMPs in CAKUT