AIM: To observe the effects of sapindoside on blood pressure,AngⅡ,Ald,ET in the blood plasma and NO in the serum in primary hypertension rat. METHODS: The primary hypertension rats were divided into 5 groups(high,middle and low sapindoside group,control group and captopril group,10 each) in a random fashion and drugs had been given by ig.for 32 days.The blood pressure was messured in the 1,3,7,32 day after administration.At the end of the 32 nd days,AngⅡ,Ald,ET in the blood plasma and NO in the serum were measured. RESULTS: Sapindoside could significantly lower the blood pressure,increase the levels of NO in serum,reduce the concentration of AngⅡ,Ald,ET in the blood plasma. CONCLUSION: Sapindoside plays an important role in decreasing the blood pressure of primary hypertension rat.

Adolescent ; Adult ; Cataract ; epidemiology ; Humans ; Middle Aged ; Occupational Exposure ; Welding ; Young Adult

Objective To investigate the correlation between the expression of tumor O (6)-methylquanine DNA methyl-tranferase(MGMT) and pathological grade,and the influence of racial factors on tumor MGMT expression levels for glioma patients. Methods Compare and analysis the correlation between the pathological grade and MGMT levels and the racial factors on MGMT expression levels by the immunohistochemical staining on the tumor specimens of 33 Uygur and 61 Han. Results The positive rate of 61 Han gliomas pations with MGMT is 45.90％ and 33 cases of the Uygur is 30. 30％ , there's no clear correlation between the racial factors and the tumor MGMT levels. (P ＞ 0. 05). Comparative the 94 patients with pathological level and tumor MGMT level, there is no clear correlation between pathologic level and MGMT pression in tumor tissues (P ＞ 0. 05 ). ConclusionThere's no clear correlation of tumor MGMT expression and pathological levels; and there's no significant effect between racial factors and expression of glioma MGMT.

OBJECTIVEEndothelial apoptosis plays an important role in the initiation of atherosclerosis. It would be useful to clarify whether activation of non-neuronal muscarinic receptor (NNMR) could prevent endothelial apoptosis and atherosclerosis. We investigated the effects of NNMR activation on regulating rat aortic endothelial cells (RAECs) apoptosis induced by homocysteine, an independent risk factor of atherosclerosis, and further studied its molecular mechanism.

METHODSRAECs were incubated using homocysteine at the concentration of 2.7 mmol/L for 36 h. RAECs were also pre-treated with carbachol or arecoline to examine their effects. RT-PCR was used to assess changes in the gene expression related to cell apoptosis.

RESULTSIncubation of RAECs with homocysteine at the concentration of 2.7 mmol/L resulted in morphologic changes, such as cellular shrinkage, membrane blebbing, chromatin condensation and margination. These could be attenuated by pretreatment with carbachol and arecoline at the concentration of 10 micromol/L for 12 h. Homocysteine induced apoptosis in RAECs and the molecular mechanisms were associated with the regulation of fas, fas-L and caspase-8 in the death receptor pathway, bcl-2, bcl-xL and bax in the mitochondrial pathway, caspase-12 in the endoplasmic reticulum pathway and caspase-3, caspase-6 and p53 as downstream effectors. Carbachol and arecoline attenuated the effects of homocysteine on genes in the death receptor pathway, in the mitochondrial pathway and in the downstream pathway. Atropine could reverse all of the effects of arecoline.

CONCLUSIONActivation of NNMR by carbacol and arecoline inhibits homocysteine-induced endothelial cell apoptosis mainly through regulation of death receptor pathway, mitochondrial pathway and downstream effectors.

Animals ; Aorta ; cytology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Arecoline ; Carbachol ; Cell Cycle ; Endoplasmic Reticulum ; metabolism ; Endothelial Cells ; cytology ; drug effects ; Homocysteine ; adverse effects ; Mitochondria ; metabolism ; Rats ; Receptors, Muscarinic ; metabolism

Vascular endothelium plays an important role in regulating vascular homeostasis. Over the past years, it has become clear that endothelial dysfunction is a key event of pathophysiological changes in the initiation and progression of injuries induced by extreme environmental factors. The present review summarizes current understanding of vascular endothelial dysfunction induced by hypoxia, cold and heat, and provides the information for prevention and treatment of environmental exposure injuries.
Endothelium, Vascular ; physiopathology ; Environment ; Humans ; Hypoxia ; physiopathology ; Temperature ; Vascular System Injuries

OBJECTIVEHigh altitue pulmonary edema (HAPE) impacts seriously people's health at high altitude. Screening of susceptibility genes for HAPE will be used for the evaluation and protection of susceptible people.

METHODSWe performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 23 HAPE patients and 17 healthy controls. GO and Pathway analysis softwares were used to analyze and draw gene network.

RESULTSThirty-nine SNPs were found to be significantly different between case and control groups (P < 10(-4)). GO and Pathway analysis of 27 genes around the 39 SNPs indicated that these genes mainly participate in the regulating of cell proliferation, regulation of nitrogen compound metabolic process and G-protein coupled receptor protein signaling pathway and so on.

CONCLUSIONIt suggests that these SNPs and genes found in this study may be associated with the susceptibility of HAPE.

Adult ; Altitude Sickness ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Hypertension, Pulmonary ; genetics ; Polymorphism, Single Nucleotide ; Young Adult

OBJECTIVETo investigate the effects of non-neuronal muscarinic receptors (NNMR) stimulation on atherosclerosis and endothelial cells activation.

METHODSAtherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 weeks. During the experimental periods, animals were received a low (7 mg/kg/d) or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the treatments, serum total cholesterol and NO levels were measured, and the aorta morphology was analyzed by hematoxylin and eosin staining. The gene expression of monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-κB activity were detected by Western blot analysis. NO production, MCP-1 secretion in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium adhesion assay were also performed after arecoline treatments.

RESULTSArecoline efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated the IκB-α degradation and P65 phosphorylation in the aortae of ApoE-/- mice. Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine methylester could abrogate these effects. Arecoline also significantly inhibited the adherence of U937 monocytes to the ox-LDL injured human umbilical vein endothelial cells, which could be abolished by atropine.

CONCLUSIONOur results indicate that arecoline attenuates the progression of atherosclerosis and inhibits endothelial cells activation and adherence by stimulating endothelial NNMR. These effects, at least in part, are due to its modulation on NF-κB activity.

Animals ; Aorta ; cytology ; Apolipoproteins E ; Arecoline ; pharmacology ; Atherosclerosis ; physiopathology ; prevention & control ; Cell Adhesion Molecules ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Disease Progression ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; I-kappa B Proteins ; metabolism ; Lipoproteins, LDL ; Mice ; Mice, Knockout ; Monocytes ; cytology ; NF-KappaB Inhibitor alpha ; Nitric Oxide ; blood ; Nitroarginine ; pharmacology ; Rats ; Receptors, Muscarinic ; physiology ; Transcription Factor RelA ; metabolism

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.
Amlodipine ; pharmacology ; Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Drug Synergism ; Heart Rate ; Hydrochlorothiazide ; pharmacology ; Hypertension ; Propranolol ; pharmacology ; Propylamines ; pharmacology ; Rats

AIMIn order to evaluate the regulatory effects of nucleotides and adenosine on ATP-sensitive potassium channel (K(ATP)) in artery smooth muscles, the effects of them on vascular relaxation induced by K(ATP) opener pinacidil(Pin) were investigated.

METHODSThe isolated endothelium- denuded aorta rings were preincubated with nucleotides or nucleotides and glibenclamide (Gli) for 10 min, the vascular relaxation induced by Pin in aorta precontracted with 20 mmol x L(-1) KCl was observed.

RESULTSAfter the isolated endothelium-denuded aorta rings were preincubated with ATP, ADP, UDP, GTP and adenosine (Ade) 100 micromol x L(-1) respectively, the vascular relaxation induced by Pin was changed as following: (1) ATP could inhibit the K(ATP) activation by Pin and enhance the blockade of K(ATP) by Gli. (2) ADP could inhibit the K(ATP) activation by Pin and attenuate the blockade of K(ATP) by Gli. (3) The regulatory effect of Ade on K(ATP) was similar with that of ADP. (4) UDP could enhance the K(ATP) activation by Pin and attenuate the blockade of K(ATP) by Gli. (5) GTP could enhance the K(ATP) activation by Pin, but had no effects on the blockade of K(ATP) by Gli.

CONCLUSIONNucleotides and adenosine, related to energy metabolism, could modulate the functions of K(ATP) in vascular smooth muscle. But their pharmacological characteristics were different.

Animals ; Aorta ; cytology ; drug effects ; Glyburide ; pharmacology ; In Vitro Techniques ; KATP Channels ; metabolism ; Male ; Muscle, Smooth, Vascular ; drug effects ; Nucleotides ; pharmacology ; Pinacidil ; pharmacology ; Rats ; Rats, Wistar ; Vasodilator Agents ; pharmacology

AIMTo study the effects of acute and chronic intermittent hypoxic exposure on the activities of Na+ , K+ -ATPase, Ca2 + , Mg2 + -ATPase of myocardial mitochondria and enzyme complexes of respiratory chain in rats.

METHODSThe activities of Na , K+ -ATPase, Ca2+ , Mg2+ -ATPase of myocardial mitochondria and enzyme complexes of respiratory chain were investigated after chronic intermittent hypoxic exposure (3000 m and 5000 m, 4 h/d, 2 w respectively) and normoxic rats were exposed to hypoxia (8000 m) for 4h.

RESULTS(1) Hypoxia had no effects on the activity of Na+, K+ -ATPase in myocardial mitochondria of rats. (2) Compared with normoxic control rats, the activity of Ca2+, Mg2+ -ATPase in myocardial mitochondria of acute hypoxic rats was reduced significantly. After chronic intermittent hypoxic exposure, its activity was increased significantly compared with that of acute hypoxic rats. (3) Compared with normoxic control rats, the activities of enzyme complex I, II and IV of respiratory chain in acute hypoxic rats were reduced significantly. After chronic intermittent hypoxic exposure, their activities were increased significantly compared with those of acute hypoxic rats. Under the same experimental conditions, hypoxia had no effects on the activity of enzyme complex III.

CONCLUSIONAfter chronic intermittent hypoxic exposure, the activities of Na+, K+ -ATPase, Ca2+, Mg2+ -ATPase of myocardial mitochondria and enzyme complexes of respiratory chain were increased significantly. These suggested that chronic intermittent hypoxic exposure could improve the functions of respiratory chain in myocardial mitochondria and keep the normal energy metabolism.

Animals ; Calcium ; metabolism ; Electron Transport ; Hypoxia ; metabolism ; Male ; Mitochondria, Heart ; enzymology ; Mitochondrial Proton-Translocating ATPases ; metabolism ; Multienzyme Complexes ; metabolism ; Potassium ; metabolism ; Rats ; Rats, Wistar ; Sodium-Potassium-Exchanging ATPase ; metabolism