Endogenous basic fibroblst growth factor is a protective factor against myocardial ischemia/reperfusion injury of rats

AIM: To observe the role of exogenous and endogenous basic fibroblst growth factor (bFGF) on myocardial ischemia/reperfusion(I/R) injury of rats.METHODS:bFGF and bFGF antiserum were applied to rat isolated I/R heart. Myocardial function, coronary effluent volume,protein and myoglobin content as well as LDH activity in coronary effluent fluid, myocardial calcium, MDA and ATP concentration as well as PKC, MAPK activity were measured. RESULTS:Compared with control, myocardial function in I/R group significantly decreased. Protein, myoglobin content and LDH activity in coronary effluent liquid as well as myocardial MDA and calcium content increased, while myocardial ATP concentration decreased(all P＜0.01). Compared with I/R group, ±LV dp/dt_max in bFGF group increased by 43% and 26%, respectively. LVEDP decreased by 40%. HRr/HRi and B/A augmented by 42% and 20%, respectively. Protein and myoglobin content as well as LDH activity lowered by 29%,30％ (all P＜0.01) and 33％ (P＜0.05) respectively. Myocardial MDA and calcium content decreased by 44% and 35%, respectively, while myocardial ATP level as well as PKC and MAPK activity increased by 34%,41％ and 10% (all P＜0.01), respectively. In bFGF antiserum group, ±LV dp/dt_max were 35% and 38% lower than those in I/R group. LVEDP increased by 93%. HRr/HRi and B/A decreased by 36% and 45%, respectively. Protein and myoglobin content as well as LDH activity augmented by 54%,96％ (all P＜0.01) and 34％ (P＜0.05) respectively. Myocardial MDA and calcium content increased by 24% and 50%, respectively, while myocardial ATP level as well as PKC and MAPK activity lowered by 28%,21％ and 8% (all P＜0.01), respectively. CONCLUSION:Endogenous bFGF is a protective factor against myocardial ischemia/reperfusion injury of rats.     

早熟大粒无核葡萄新品种‘超级无核’

 ‘超级无核’葡萄系从美国引进葡萄新品种‘Superior Seedless’优选单株培育出的优良品种。无核、大粒、早熟、优质、早实、丰产、生长势强健、耐病、耐不利栽培条件, 是适合高温、高湿、少日照地区栽培的无核葡萄新品种。     

Alteration of cardiac sarcoplasmic reticulum function in vitamin D3-induced calcium overload rats

AIM:To study alterations of cardiac sarcoplasmic reticulum (SR) function in vitamin D₃-induced calcium overload rats. METHODS: The Ca-overload rat models were prepared by vitamin D₃ plus nicotine. Cardiac SR was seperated by centrifuging. The measurement of SR Ca²⁺uptake and Ca²⁺ release activities were preformed by the Millimore filtration technique. Specific SR -ryanodine binding capacity was measured by radioligand method. RESULTS: Compared with control,myocardial calcium content in calcium overload rats increased by 78%(P＜0.01), SR Ca²⁺ uptake and Ca²⁺ release activities decreased by 64% and 40% respectively(P＜0.01),and in the meantime ,the Ca²⁺-ATPase activity decreased by 65%(P＜0.01).Maxmum value for -ryanodine binding decreased by 51%(P＜0.01). CONCLUSION:The function of cardiac SR in calcium-overload rats was decreased.     

The renal L-arginine/nitric oxide pathway and erythrocyte L-arginine transport in spontaneously hypertensive rats

AIM: To investigate the changes of the renal L-arginine /nitric oxide pathway and the relationship of L-arginine transport between kidney and erythrocytes in spontaneously hypertensive rat (SHR). METHODS: Sixteen week old SHR, 16 week old SHR with captopril (CAP) treated for four weeks and 16 week old WKY rats were used in the experiment. L-arginine transport, NO synthase(NOS) activity, nitrite and cyclic GMP (cGMP) content were measured in renal tissue or erythrocytes. RESULTS: In the renal tissue, compared with that of WKY group, the Vmax of high-or low-affinity L-arginine transporter, NOS activity, NO₂^- and cGMP content of SHR group were significantly decreased (P＜0.01 or P＜0.05). The Vmax of high-affinity L-arginine transporter and NOS activity of CAP group were significantly enhanced as compared with SHR group (+90%, P＜0.01; +58.6%, P＜0.05). The NOS activity had significant positive correlation with the Vmax of high-affinity L-arginine transporter (r=0.585, P＜0.05). The changes of erythrocyte L-arginine transport were the same as that of kidney. The Vmax of SHR group was lower than that of WKY group (-30%, P＜0.01), and the Vmax of CAP group was higher than that of SHR group (+26.5%, P＜0.01). Km was not significantly changed. There is a positive correlation between the Vmax of L-arginine transport in erythrocyte and the Vmax of high- or low-affinity L-arginine transporter in renal tissue, (r=0.8434, P＜0.01, high-affinity; r=0.5255, P＜0.05, low-affinity). CONCLUSION: There existed a functional inhibition in L-arginine/nitric oxide pathway in the kidney of SHR. It can be recovered obviously by captopril treatment. The changes of L-arginine transport in kidney coincide with that in erythrocyte.     

Endothelin receptor antagonist BQ123 inhibits calcification in vascular smooth muscle cells induced by β-glycerophosphate

AIM:To observe the effect of endothelin receptor antagonist (BQ123) on calcification in rat vascular smooth muscle cells (VSMCs) in vitro. METHODS:Calcification of cultured rat VSMCs was produced by incubation with β-glycerophosphate. Calcium content, Ca2+ deposition and alkaline phosphatase activity were analyzed to estimate the extent of calcification. The DNA synthesis was detected by ［3H］ -TdR and ［3H］-Leu incorporation. Osteopontin (OPN) mRNA was measured by competitive quantitative RT-PCR. Content of ET was measured by radioimmunoassay (RIA). RESULTS:The results showed that compared with the control, the content of calcium, ［45Ca2+］ uptake and alkaline phosphatases activities in calcified VSMCs increased by 118%, 174% and 7-fold (all P<0.01), respectively. The expression of OPN mRNA in calcified VSMCs was up-regulated by 86% (P<0.01). The calcified VSMCs grew rapidly, in which ［3H］-TdR and ［3H］-Leu were elevated by 71% and 35%. The content of ET in calcified VSMCs medium was increased by 35% as compared with control. Furthermore, calcified VSMCs plus BQ123 groups obviously relieved degree of calcification, of which calcium content, Ca2+ deposition and alkaline phosphatase activities were 33%, 37%, 40% lower than those in calcified VSMCs (P<0.01), respectively. The expression of OPN mRNA was down-regulated by 25% (P<0.01) and significantly inhibited VSMCs proliferation. CONCLUSION:BQ123 reduces VSMCs calcification, suggesting that ET promotes calcification in VSMCs mainly by ET/ ETA receptor pathway.     

Effect of altitude hypoxia on glutamate,aspartate and NOS in the rat hypothalamus

AIM: To investigate the effects of external counterpulsation (ECP) on nitric oxide (NO) and nitric oxide synthase (NOS) and the expression of NOS gene in myocardial infarction canines. METHODS: Nineteen healthy dogs were randomly divided into three groups ie. controls, ischemia group, ischemia and ECP group. Serum NO concentrations and myocardium NO levels and NOS specific activity were determined by modified nitrate reductase method. The protein synthesis of sub-type NOS including inducible NOS (iNOS) and endothelial NOS (eNOS) of myocardial tissue were also determined by immunohistochemical method. The constitutive NOS (cNOS) mRNA was measured via in situ hybridization. RESULTS: 120 and 180 minutes after the ligating of LAD, serum NO concentration in ECP groups were higher than those in ischemic groups (P＜0.05). The NO levels and NOS specific activity in myocardium of ischemic dogs were lower than those in controls and ECP group (P＜0.05). Protein synthesis of iNOS increased and that of eNOS decreased in ischemic myocardium. But ECP could control the protein synthesis of iNOS, and increase that of eNOS. Further studies showed that the expression of cNOS mRNA decreased in ischemic myocardial tissue, ECP might promote the expression of it and regulate NOS in the gene level. CONCLUSION: The results suggested that it was one of the most important mechanisms through raising the NO levels to protect ischemic myocardium in ECP.     

Down-regulation of glutamyl cysteine cystathionine-lyase/hydrogen sulfide system in rat cardiovascular calcification

AIM：To observe the changes of cystathionine-lyase/hydrogen sulfide (CSE/H2S) in vivo in vascular calcification and to explore the role of CSE/H2S in vascular calcification.METHODS：Vascular calcification model in rats was induced by administration of vitamin D3 plus nicotine.The extent of calcification was estimated by assaying calcium content.［45Ca2+］ deposition and alkaline phosphatase (ALP) activity were detected.CSE mRNA amount was determined by using competitive quantitative RT-PCR.The content of H2S and activity of CSE in the plasma and cardiovascular tissues were also determined with biochemical methods.RESULTS：Calcium content in myocardium increased by 3.8 folds in a calcification model.Compared to control,calcium content,［45Ca2+］ accumulation and ALP activity in calcified arteries increased by 6.8,1.4,and 1.9 folds,respectively (P＜0.01).H2S contents in plasma,myocardium and aorta were 39%,39% and 31% lower than those in control group (P＜0.01).The gene expression of CSE was down-regulated in myocardium and aorta.Compared to control group,the amount of CSE mRNA in myocardium and calcified aorta were decreased by 28% and 36%,respectively (P＜0.01).The activity of CSE was 56% and 53% lower than that in control (P<0.01).CONCLUSION：The production of H2S,the gene expression and activity of CSE are down-regulated in the cardiovascular calcification,suggesting that the decrease in H2S production plays a role in the pathogenesis of vascular calcification.     

Changes of heme oxygenase-carbon monoxide system-in vascular calcification in rats

AIM:To investigate the change of heme oxygenase (HO)-carbon monoxide (CO)-cyclic guanosine monophosphate (cGMP) pathway in vascular calcification, to clarify the cellular and molecular mechanimsm in vascular calcification.METHODS:Vascular calcification model was established in rats by using vitamin D₃ and nicotine. The relative content of HO-1 mRNA, immunochemistry (IH) for HO-1, HO activity, HbCO formation and content of cGMP in aorta were measured.RESULTS:Compared to those of control rats, the HO-1 mRNA level in vessels of rats in VDN group(vascular calcification group) were decreased by 34.9% (P＜0.05);expression of HO-1 protein were decreased too, there were trace positive staining of HO-1 in the endothelium, and no obvious immunoreactivity in the medial layer;HO-1 activity was decreased by 60.6% (P＜0.01), CO concentration was decreased by 53.9% (P＜0.01) and cGMP content was decreased by 77.1% (P＜0.01) in vessels of rats in VDN group.CONCLUSION:There were obvious down regulation in HO-CO-cGMP pathway in calcified vessels.     

Effects of PPARβ and NO on high glucose and insulin-induced cardiomyocyte hypertrophy

AIM: To investigate the role of peroxisome proliferator-activated receptor β(PPARβ)-nitric oxide(NO) signal pathway in cardiomyocyte hypertrophy induced by high glucose(25.5 mmol/L) and insulin(0.1 μmol/L)(HGI). METHODS: The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by measuring the cell surface area, protein content, and the mRNA expression of atrial natriuretic factor(ANF). The mRNA and protein expression were measured by real-time PCR and Western blotting, respectively. The activity of NO synthase(NOS) and NO content were measured by a reagent kit through ultraviolet spectroscopy. RESULTS: HGI induced profound change of hypertrophic morphology, and significantly increased the cell surface area, protein content and mRNA expression of ANF(P<0.01), but decreased the expression of PPARβ at mRNA and protein levels(P<0.05). At the same time, the expression of inducible NOS(iNOS) was obviously elevated(P<0.01), which occurred in parallel with the rising NOS activity and NO concentration(P<0.01). GW0742(1 μmol/L), a selective PPARβ agonist, inhibited the cardiomyocyte hypertrophy induced by HGI(P<0.01), and up-regulated the expression of PPARβ at both mRNA and protein levels. Meanwhile, GW0742 also inhibited the increases in iNOS expression, NOS activity, and NO content induced by HGI, which were abolished by GSK0660(1 μmol/L), a selective PPARβ antagonist(P<0.01). CONCLUSION: PPARβ down-regulation and the following iNOS-NO activation are involved in the cardiomyocyte hypertrophy induced by HGI.     

Effect of chronic hypoxia on L-Arginine/nitric oxide pathway in rat pulmonary artery

AIM: To study the effect of chronic hypoxia on L-Arginine/NO pathway in rat pulmonary artery. METHODS: Changes in pulmonary artery L-Arginine(L-Arg) transport, nitric oxide synthase (NOS) activity, plasma nitrite level and L-Arg level in HPH rats were investigated. RESULTS: (1) The mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) of HPH group were higher than those in control group (P＜0.01). (2) Plasma L-Arg level in HPH group was not significantly changed. (3) At low (0.2 mmol/L)or high(5.0 mmol/L)concentration of L-Arg, the velocity of L-Arg transport in HPH group was lower than that in control group (P＜0.05 or P＜0.01). (4) The activity of pulmonary artery tNOS, iNOS and cNOS in HPH group were increased by 38.0%, 32.8% and 53.0%, respectively (P＜0.01), compared with control group. (5) Plasma NO level of HPH group was decreased, which was negative correlation to mPAP and RV/LV+S (P＜0.01). CONCLUSION: The decrease of nitric oxide generation might result from L-Arg transport injury, while pulmonary artery tNOS, iNOS and cNOS activity were enhanced during chronic hypoxia.     

The relationship between nitric oxide and gastric mucosal injury induced by reserpine in rats

AIM: To study the relationship between nitric oxide (NO) and gastric mucosal injury induced by reserpine in rats. METHODS: Sixteen healthy male Wistar rats were randomly divided into control group and experimental group (n=8). NO contents and malondialdehyde(MDA) contents in plasma, gastric mucosa of the rats were respectively determined with Cadmium-reduct plus Greiss and TBA; nitric oxide synthase in gastric walls of the rats were observed using NADPH-diaphorase histochemistry and quantitatively measured with image analyzer. RESULTS: The NO contents in both plasma and gastric mucosa of experimental group were significantly lower than that in control group (P＜0.01),but their MDA contents were both higher than that in control group(P＜0.05,P＜0.01);the densities and A values of nitric oxide synthase (NOS)-positive nerve-cells and nerve fibers in gastric walls of experimental group were all obviously lower than that in control group (P＜0.05,P＜0.01). CONCLUSION: The mechanism of the reserpine-induced gastric mucosal injury in rats might be related to NO insufficiency arisen from the inhibition of NOS activity in NANC nerves in gastric wall,which might weaken the protection to gastric mucosa.     

Role of endogenous nitric oxide synthase inhibitor in erectile dysfunction of diabetic rats

AIM: To investigate the role of nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in erectile dysfunction of diabetic rats.METHODS: Type 2 diabetic rat model was established by 4 weeks of high-fat diet plus a single intraperitoneal injection of streptozotocin and continued high-fat diet feeding for 8 weeks. Corpus cavernosum was isolated from the rats under anesthetization, and the endothelium-dependent relaxation response to acetylcholine (ACh) was tested in an organ chamber to reflect erectile function. The level of ADMA in serum was detected. The NOS activity, nitric oxide (NO) content and cyclic guanosine monophosphate (cGMP) content in corpus cavernosum were measured. The protein expression of ADMA-NOS-NO pathway-related molecules and phosphodiesteras 5 (PDE5) in the corpus cavernosum was detected by Western blot. Superoxide dismutase activity and malondialdehyde content were analyzed to evaluate oxidative stress.RESULTS: Elevated blood glucose and lowered insulin sensitivity were observed in the diabe-tic rats, indicating that type 2 diabetic rat model was successfully established. Compared with control group, the relaxation response to ACh of corpus cavernosum from diabetic rats was significantly decreased, which was accompanied with the elevation of serum ADMA level and reduction of NOS activity, NO content and cGMP content in the corpus cavernosum. The protein expression of ADMA-generating enzyme protein arginine methyltransferase 1 was up-regulated, while ADMA-metabolic enzymes dimethylarginine dimethylaminohydrolases 1 and 2, and ADMA-targeting enzymes endothelial NOS and neuronal NOS were down-regulated. The protein expression of PDE5 was up-regulated, accompanied with an increase in oxidative stress in the corpus cavernosum of diabetic rats. Incubation of isolated corpus cavernosum from normal rats with NOS inhibitor ADMA induced the similar relaxation dysfunction of corpus cavernosum response to ACh and decreased NO and cGMP contents in diabetic rats.CONCLUSION: Elevated endogenous NOS inhibitor ADMA plays an important role in erectile dysfunction of diabetic rats. The underlying mechanism may be related to the reduction of NO production and the increase in oxidative stress.     

Dynamic changes of the concentration of nitric oxide in ischemic myocardium and its mechanism

AIM: The study was undertaken to explore the dynamic changes of the concentration of nitric oxide(NO) in ischemic myocardium and its mechanism.METHODS: In vivo myocardial ischemia of mice and in vitro perfused isolated heart of rat were used in the experiment. The effects of severity and time of ischemia on NO production, NOS activity and mRNA were examined, respectively. RESULTS: There was a considerable difference (P<0.01) in the concentration of NO between ischemia group [(9.12±1.40) μmol/L] and control group [(20.16±1.67) μmol/L] after Pit(30 U/kg) administration, and the concentration of NO of ischemic group significantly decreased [(9.17±1.33) μmol/L] compared with control group [(19.90±1.95) μmol/L] after 30 minutes of ischemia. Also, the concentration of NO after Pit(20 U/L) administration in K-H and 15 min of ischemia was (15.41±2.00) μmol/L and (15.09±2.00) μmol/L respectively in vitro, significantly lower than control group [(23.83±2.33) μmol/L and (23.63±2.52) μmol/L]. In addition, compared with control group, the number of NOS positive cells, NOS activity as well as mRNA expression in atrial muscle and ventricular muscle of ischemic group were markedly reduced, respectively. CONCLUSION: Myocardial ischemia could reduced the NO level in myocardium, down-regulation of NOS mRNA could be the possible mechanism.     

Changes of L-arginine,NOS/NO pathway in adventitia of rats with sepsis

AIM: In this study, we aimed to explore the alteration and pathophysiological significance of the L-arginine (L-Arg)/NOS/NO pathway in the adventitia of rats with sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP). Rat cardiac function was determined. NO generation, NOS activity and L-Arg transport were measured. The iNOS mRNA levels was determined by using RT-PCR. RESULTS: Cecal ligation and puncture induced severe sepsis with severe low glucose, high lacticemia and cardiac function inhibition. The iNOS activity was increased by 2.8-fold compared with controls (P<0.01) and the iNOS mRNA level was elevated-6-fold (P<0.01). The NO level in plasma and incubation media (incubation for 40 min) in the sepsis group was increased by 144% and 273% (both P<0.01), respectively. CONCLUSION: The results demonstrated that the L-Arg,NOS/NO pathway was activated in vascular adventitia of rats with sepsis shock. The aortic adventitia L-Arg/NOS/NO pathway might play an important role in the pathogenesis of sepsis and septic shock.     

Effects of hyperbaric oxygen and cyclosporin A on thelevels of active oxygens and nitric oxide in spleens of skin transplanted mice

AIM: To study effects of hyperbaric oxygen (HBO) and cyclosporin A (CsA) on the contents of active oxygens and nitric oxide (NO) in spleens of skin transplanted mice. METHODS: The donor mice BALB/C and receptor mice C₅₇BL/6 were tested for skin transplantation. The HBO group mice were treated with 99.2% oxygen under 0.25 MPa for 1.5 hours, while CsA group mice were treated with CsA 0.5 mg·kg^-1·d^-1 by abdomen injection. After 14 days, the spleen were extracted the contents of malondialdehyde (MDA) and NO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and NO synthases (NOS) were determined. RESULTS: (1) Compared with the control group, the transplantation group, HBO group and CsA group have markedly increased the content of MDA and the activities of GSH-PX and CAT; Compared with the transplantation group, the CsA group have markedly increased activity of SOD and reduced activities of GSH-PX and CAT; the HBO group have markedly reduced the activity of GSH-PX and increased the activities of CAT and SOD (P<0.01). (2) Compared with the control group, the transplantation group have markedly increased the content of NO and the activity of NOS; Compared with the transplantation group, the HBO group have markedly increased the activity of NOS and reduced the content of NO (P<0.01); The content of NO and the activity of NOS in CsA group was not changed significantly. CONCLUSION: In the lymphocytes of the transplantation group, the peroxidation is intensified, and the content of NO and the activity of NOS increased. HBO and CsA may activate the systems of oxidation/antioxidation and NO/NOS in spleen, which may be related to their mechanism of inhibition rejection.     

Endogenous nitric oxide synthase inhibitor increase skeletal muscle contractility and mitochondria biosynthesis in 4-week running rats

AIM: To observe the effect of endogenous nitric oxide synthase(NOS) inhibitor asymmetric dimethylarginine(ADMA) and its signaling pathways on NO levels and skeletal muscle contractility in 4-week running rats. METHODS: The 4 weeks running rat model was established. The twitch tension, tetanic tension and the fatigue test of soleus muscle induced by electrical stimulation ex vivo were detected. The ATP content, mitochondrial DNA levels and the mRNA expression of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), nuclear respiratory factor(NRF) were measured to reflect the mitochondrial function and biosynthesis in the skeletal muscle. Serum ADMA concentration was detected by high performance liquid chromatography. The endogenous ADMA enzymes PRMT1 and 2 subtypes of ADMA metabolism enzyme DDAH, 3 subtypes of NOS protein expression in the skeletal muscle were determined by Western blot. NOS activity and nitric oxide(NO) content were analyzed by colorimetric method. RESULTS: Compared with normal control group, the twitch tension, tetanic tension and the anti-fatigue capability of soleus muscle in running group were significantly enhanced, ATP content, mitochondrial DNA content and the mRNA expression of PGC-1α and NRF were significantly increased(P<0.01). In addition, the protein expression of constitute type NOS(cNOS) and NOS activity were significantly increased(P<0.01), but the increase in NO content was relatively smaller in soleus muscle in exercise group(P<0.05). Moreover, serum ADMA concentration in running group was increased, while the DDAH2 expression in skeletal muscle was decreased.CONCLUSION: Short-term endurance exercise enhances the twitch tension, tetanic tension and fatigue resistance of soleus muscle. The mechanism may be that increased cNOS expression feedbacks to increase ADMA concentration, thus maintaining the increase in NO synthesis at a relatively low level, and resulting in promoting skeletal muscle mitochondria biosynthesis and mitochondrial function.     

Changes in endogenous nitric oxide and effects of inhaled nitric oxide on pulmonary artery hypertension in chronically hypoxic rats

AIM: To investigate the role of nitric oxide (NO)in the development of chronically hypoxic pulmonary artery hypertension (PAH) and the hemodynamic effects of inhaled NO on pulmonary circulation. METHODS: 67 male adult SD rats were randomly divided into 7 groups: (1) control (n=9);(2) chronically intermitent hypoxia (CIH, 6 h/d, 7 d/w) 1 week(n=7); (3) CIH 2 weeks (n=11); (4) CIH 3 weeks (n=11); (5) CIH 1 week+L-NAME (NO synthase inhibitor, 30 mg/kg, by gavage, n=10); (6)CIH 3 weeks+L-Arg (NO precursor, 10 mg/kg, by gavage, n=9); (7) CIH 3 weeks+inhaled NO (0.0004% for 20 min, n=10) to determine the mean pulmonary artery pressure (MPAP), weigh the right ventricle (R) and ventricular segment plus left ventricle (S+L), and calculate R/(S+L) (g/g) and R/Wt (Wt: body weight, g/kg). RESULTS: 1.MPAP increased compared with control when CIH 1 week, reaching the highest when CIH 2 weeks; R/(S+L) and R/Wt also increased notably when CIH 1 week (P＜0.01); 2. The level of plasma NO₂^-/NO₃^- elevated significantly when CIH 2 weeks, but fell when CIH 3 weeks; the content of plasma ET-1(endothelin-1) also increased significantly. The level of plasma ET-1 correlated with R/(S+L) and R/Wt, r=0.43 and 0.46, respectively, both P＜0.01; 3. The level of plasma NO₂^-/NO₃^- droped 33.2 % (P＜0.01) after treatment with L-NAME, with R/(S+L) increasing 15.2 % (P＜0.05); 4. L-Arg decreased the MPAP 17.8 %(P＜0.01). CONCLUSION: The endogenous NO release increases at early stage (1-2 weeks) of chronic hypoxia, but falls at the prolonged stage; the elevated level of plasma ET-1 possibly plays an important role in remodeling of chronically hypoxic pulmonary vessels and ventricle; inhaled NO significantly decreases the chronically hypoxic PAH.     

Changes in L-arginine/nitric oxide pathway of the aorta in septic shock rats

AIM:To observe the change of nitric oxide (NO) generation system in the vascular adventitia, media and intima in septic shock rats.METHODS:The septic shock model was made in rats by caecal ligation and puncture. The intima, media and adventitia of the rat aorta were separated. NO production (NO₂^-), nitric oxide synthase(NOS) activity and L-arginine (L-Arg) transport were measured, separately. Inducible NOS (iNOS) distribution was detected by immunohistochemistry.RESULTS:Both in early and late stage of septic shock, NO₂^- from the intima was decreased by 66.1% and 78.9%(P<0.01), while NO₂^- from the media was increased by 1.1 and 2.2 folds(P＜0.01), and the adventitia 9.6 and 18.6-fold (P＜0.01), as compared with the sham group, respectively. The changes of NOS activity and the L-arginine transport in the intima, the media layer and the adventitia of the aorta in the septic shock rat paralleled with that of NO₂^- in these tissues. The results of iNOS immunohistochemistry showed that there were obviously positive staining in the media layer and adventitia, especially the adventitia of the rat aortas in septic shock, as compared with that in the sham control.CONCLUSIONS:During septic shock, NO production in the aortic intima was progressively suppressed. However, it was progressively increased in the aortic medial layer and adventitia, especially the adventitia with shock processes. These changes result from different changes of L-arginine transport, NOS activity and its expression in three layers of the aorta from the septic shock rat.     

Effect of taurine on L-arginine/NO pathway in erythrocytes of rats of hypertension with insulin resistance induced by fructose

AIM and METHODS:The present study observed the change of L-arginine(L-Arg)/Nitric oxide(NO)pathway in ergthrocytes in hypertension with insulin resistance rat induced by fructose and the effect of taurine on L-Arg/NO pathway.RESULTS:Drinking 4%fructose, while inducing blood pressure, glucose and plasma insulin contents increase, obviously decreased the maximal velocity of L-Arg transport about 31%and 37%(P<0.01), more than that of control group in total and Y⁺ carrier, the NO synthase(NOS)activity, nitrite(NO₂^-)content and cyclic guanylate monophosphate(cGMP)level more than that of control group, but obviously enhanced Michaelis Constant(Km)about 35%and 30%(P<0.01)more than that of control group in total and Y⁺ carrier transport.The taurine treatment significantly counteracted the above changes.CONCLUSION:There exists a functional disturbance in L-Arg/NO system in the erythrocyte of hypertension rats with insulin resistance, but taurine can obviously enhanced the maximal velocity of L-Arg transport and NOS activity.Thus, it appears that taurinemay have vital value in the treatment of hypertension with insulin resistance.     

Septic shock down-regulates L -arginine /NOS /NO pathway of platelet and aortic intima in rats

AIM: To investigate alteration and cross link of the aortic and platelet endogenous L -arginine/NOS/NO pathway induced by septic shock.METHODS: The septic shock model was made in rats by caecal ligation and puncture. NO^-₂/NO^-₃ production released from aortic and platelet was measured with Greiss assay. NOS activity and L-arginine transport activity were detected by isotope tracer method. RESULTS: Both in early and late stage of septic shock, NO^-₂/NO^-₃ production, NOS activity, and the L-arginine transport from the aorta intima and platelets were obviously decreased, while those of the aorta media and adventitia were obviously increased (P<0.01), but high-affinity L-arginine transport activity from the aorta intima and platelets was increased in early stage of septic shock (P>0.05 and P<0.05), as compared with the sham group, respectively. The inhibitory effects of NO^-₂/NO^-₃, NOS activity and the L-arginine transport showed a positive correlation between platelet and aortic intima (P<0.01). CONCLUSION: Septic shock down-regulates endogenous L-arginine/NOS/NO pathway in aortic intima and platelet, up-regulates L-arginine/NOS/NO pathway of aortic media and adventitia. Detection of the alteration of endogenous L-arginine/NOS/NO pathway in platelet might act as an indirect method to assess the endothelial dysfunction involving the pathogensis of septic shock.