AIM: To investigate the effect of L-phenyla lanine on vascular remodeling in hypertensive rats. METHODS: Vascular remodeling was measured by laser scanning conf ocal microscopy (LSCM) in mesenteric resistance arteries isolated from spontaneo usly hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat. The effect of L-phenylalanine on the hypertensive vascular remodeling was observed. The thi rd most distal first-order branches of mesenteric resistance arteries from SHR a nd WKY were studied. The arteries were fixed under pressure. The segments were s tained with the nuclear dye propidium iodide. The diameter, wall thickness and o rientation angle of smooth muscle cells were measured with LSCM. RESULTS: Compared with WKY, SHR arteries showed: (1) smaller lum en, (2) increased wall thickness, (3) disorganized orientation angle of smooth m uscle cells. L-phenylalanine treatment induced specific changes in the lumen, wa ll thickness and the orientation angle of smooth muscle cells. CONCLUSIONS: Hypertension induces vascular remodeling of the bra nches of mesenteric arteries from SHR. L-phenylalanine inhibits the vascular rem odeling process of hypertension.

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.

Objective　To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). Methods　The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR-phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3 H-thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca2+ influx was measured in counts/min of 45　 CaCl2 after incubating it with 5 different concentrations of phenylalanine and the intracellular ［Ca2+］i by Fura-Ⅱ/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen α2(Ⅰ)cDNA. The tyrosine hydroxylase (TH) activity was measured by high-performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of pharmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3 H-L-phe (1*!ml/kg) by PK-GRAPH Program for kinetic calculation. The 3　H-L-phe uptake by CSMCs after incubating for difinite intervals was also detected and compared. Results　Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearranged cardiovascular structure was much improved. The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhibition of collagen α2(Ⅰ)cDNA, c-fos and c-myc expression. Other mechanisms may include decrease of intracellular ［Ca2+］i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus. Besides, partial recovery of phenylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness. Conclusions　Phenylalanine intervention could exert a definite anti-hypertension and anti-cardiovascular remodeling effects on SHRs like seen in human essential hypertension. Its mechanisms might be related to direct inhibition of growth in the cardiovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellular ［Ca2+］i.

Objective　To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH). Methods　1. L-(2, 3D3)-leucine, L-(2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n=10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n=12, FS+) and those without genetic predisposition of EH and stroke (n=12, F) groups. 2. By comparing the radioactive counts of ［3H］-phe, and their weight transformation in blood after 1.5?Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of ［3H］-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were compared. Results　A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular tissue. Conclusion　A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies.

Two main impact factors on accuracy of electronic balance are discussed based on its working principle:acceleration of gravity and temperature variation.Through analysis of interacting variables in acceleration of gravity and electronic balance measurement results,the method of builtin standard weight compensation and its shortages are brought forward and attach the compensation method on weight calibration.The impacts on temperature change for the electronic balance measurement are analyzed,which proposes a method to eliminate these factors.

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.
Animals ; Anti-Arrhythmia Agents ; administration & dosage ; Antibiotics, Antineoplastic ; Carbazoles ; administration & dosage ; Cardiomyopathies ; chemically induced ; physiopathology ; prevention & control ; Doxorubicin ; Heart Rate ; drug effects ; Male ; Metoprolol ; administration & dosage ; Oxidative Stress ; drug effects ; Propanolamines ; administration & dosage ; Rabbits ; Treatment Outcome ; Ventricular Fibrillation ; chemically induced ; physiopathology ; prevention & control

Objective:To investigate the infarct size and its related factors in patients with anterior choroidal artery (AchA) territory infarction.Methods:From April 2016 to April 2018, consecutive patients with acute AchA territory infarction hospitalized in the Department of Neurology, the Affiliated Shuyang Hospital of Xuzhou Medical University were enrolled retrospectively. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the disease at baseline, and the Diffusion-Weighted Imaging (DWI) was used to determine the side, location, size, and morphology of the infarct lesions. The patients were divided into small infarction group (<20 mm) and large infarction group (≥20 mm). Multivariate logistic regression analysis was used to determine the independent risk factors for infarct size. Results:A total of 100 consecutive patients with acute AchA territory infarction were enrolled, including 86 (86.0%) in small infarction group, 14 (14.0%) in large infarction group. Based on the NIHSS score, there were 89 patients with mild stroke, 9 with moderate stroke, and 2 with severe stroke. According to DWI, 69 patients (69.0%) had long cord-like infarcts and 31 (31.0%) had other shapes of infarcts. The baseline NIHSS score (7.0 [2.0-10.5] vs. 3.0 [2.0-4.0]; Z=2.353, P=0.019) and the proportion of patients with severe stroke (14.3% vs. 0%; P=0.018), the infarcts in posterior part of periventricular area (85.7% vs. 57.0%; χ2=4.180, P=0.041) and medial globus pallidus (21.4% vs. 4.7%; χ2=5.206, P=0.023), and cord-like infarction (92.9% vs. 65.1%; χ2=4.332, P=0.037) in patients of the large infarction group were significantly higher than those of the small infarction group; leukocyte count (7.7±1.7×10 9/L vs. 6.6±1.8×10 9/L; t=2.214, P=0.036) and platelet count (234.5±39.5×10 9/L vs. 198.0±49.4×10 9/L; t=2.618, P=0.010) were significantly higher than those of the small infarction group; the proportion of patients with sensory impairment was significantly higher than that of the small infarction group (50.0% vs. 24.4%; χ2=3.908, P=0.048). Multivariate logistic regression analysis showed that platelet count (odds ratio 1.018, 95% confidence interval 1.000-1.621; P=0.044) and stroke severity (odds ratio 18.245, 95% confidence interval 1.534-217.052; P=0.022) were significantly and positively correlated with the infarct size. Conclusion:The related factors of the infarct size in patients with AchA territory infarction included sensory impairment, baseline NIHSS score, stroke severity, morphology and location of infarct lesions, and leukocyte and platelet counts, of which platelet count and stroke severity were independently positively correlated with the infarct size.