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Aim To investigate the role of eNOS/PKG- 1 pathway in L-arginine (L-arg) intervention in right ventricular remodeling induced by monocrotaline (MCT) in Sprague Dawley (SD) rats with the aid of the tool medicine L-NAME. Methods Twenty SD rats were randomly divided into control group, MCT group, L-Arg group and L-Arg + L-NAME group. The general condition of rats was observed; the right ventricular pressure of rats was measured by right heart catheterization; the rats and the right ventricle were weighed and the right ventricular mass index was calculated; the morphological changes of the right ventricular were observed by H&E staining; the protein expressions of cTnl, eNOS and PKG-1 were detected by Western blot in the right ventricular. Results Compared with control group, right ventricular max pressure and right ventricular mass index significantly increased ( P < 05) ; the weight of rats in MCT group was significantly reduced ( P < 0. 05); the right ventricular myocytes were hypertrophic, disordered and infiltrated with inflammatory cells; the protein expression of cTnl was obviously up-regulated ( P < 0. 05 ) ; the protein expressions of eNOS and PKG-1 were significantly down- regulated ( P < 0. 05 ) . L-arg could significantly improve the above changes ( P < 0. 05 ). However, the effects of L-arg were inhibited by eNOS inhibitor L- NAME. Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT, and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.
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OBJECTIVE@#To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.@*METHODS@#Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP@*RESULTS@#Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP@*CONCLUSIONS@#Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP
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Objective To study the effect of recombinant human relaxin (RLX) on regulating the protein kinase G (PKG) in myocardial tissue taken from a rabbit diastolic heart failure (DHF) model.Methods A DHF model of rabbits was established by constricting their abominal aorta.Twenty-eight New Zealand rabbits were randomly divided into sham operation group (n =6),DHF group (n=6),30 μg/kg · d RLX group (n=8),98 μg/kg · d RLX group (n=8).The animals were treated with RLX for 2 weeeks.Serum samples were taken at week 10 after operation for measuring the serum levels of BNP,RLX,3-NT,NO,cGMP and PKG by ELISA.Results The serum levels of BNP and 3-NT were significantly higher while those of NO,cGMP and PKG were significantly lower in DHF group,30 μg/kg · d RLX group and 98 μg/kg · d RLX group than in sham operaion group (P＜0.05).The serum levels of NO,cGMP and PKG were significantly higher while those of 3-NT were significantly lower in 98 μg/kg · d RLX group than in DHF group (P＜0.05).Conclusion Large RLX dose alleviates the left ventricular diastolic function and oxidative stress,increases the bioavailability of NO and the activity of PKG through the signal pathaway of NO,cGMP,PKG,and can thus prevent myocardial fibrosis and improve the left ventricular diastolic function in DHF rabbits.
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Objective To investigate the effect of specific cGMP-dependent protein kinase G (PKG) inhibitor (D)-DT-2 on the contractile function of rat vascular rings after being exposed to lipopolysaccharide (LPS).Methods The experiment was performed in 2 parts.Part Ⅰ:The Sprague-Dawley rat thoracic aortic rings were randomly divided into 3 groups (n =5 each):KH group,DT-2 group and (D)-DT-2 group.KH,DT-2 and (D)-DT-2 were added to the aortic ring after being dilated with 8-Br-cGMP 50 μmol/L for 25 min and the changes in tension of vascular rings were measured.Part Ⅱ:The rat thoracic aortic rings were randomly divided into 4 groups (n =5 each):control group,LPS group,LPS-DT2 group and LPS-(D)-DT2 group.After being incubated with LPS for 3 h in vitro.The Emax and EC50 were compared among the 4 groups.Results Part Ⅰ:Both DT-2 and (D)-DT-2 could contract the vascular rings dilated with 8-Br-cGMP and the Emax was significantly higher in (D)-DT-2 group than DT-2 group (P ＜0.05).Part Ⅱ]:Both DT-2 and (D)-DT-2 significantly improved the contractile function of vascular ring after being exposed to LPS.Emax was significantly higher,while EC50 was lower in groups DT-2 and (D)-DT-2 than in LPS group (P ＜0.01).Emax was significantly increased,while EC50 was decreased in LPS-(D)-DT-2 group as compared with LPS-DT-2 group (P ＜ 0.05).Conclusion PKG inhibitor can improve the contractile function of the vascular rings incubated with LPS and the efficacy of (D)-DT-2 is better than DT-2 in recovering the vascular reactivity.
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Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (Icap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on Icap. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on Icap. The PKG inhibitor KT5823 prevented the inhibition of Icap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.
Subject(s)
Animals , Humans , Rats , Benzoates , Carbazoles , Cyclic GMP-Dependent Protein Kinases , Ganglia, Spinal , Guanosine , Guanylate Cyclase , Hemoglobins , Imidazoles , Neurons , Nitric Oxide , Nitroprusside , Penicillamine , Phosphotransferases , Proteins , Receptors, Cytoplasmic and Nuclear , Sensory Receptor Cells , Spinal Nerve Roots , Tissue DonorsABSTRACT
AIM: To observe the regulatory effects of Rho-kinase,PKC and PKG on calcium sensitivity of vascular smooth muscle in hemorrhagic shock in rats.METHODS: The superior mesenteric artery(SMA) from hemorrhagic shock model of rat was adopted to assay the calcium sensitivity via observing the contraction initiated by Ca~(2+) under depolarizing conditions(120 mmol/L K~+) with isolated organ perfusion system.Rho-kinase agonist Ang-Ⅱ and inhibitor fasudil,PKC agonist PMA and inhibitor staurosporine,PKG agonist 8Br-cGMP and inhibitor KT-5823 were used as tool agents to study the regulatory effect of Rho-kinase,PKC and PKG on the calcium sensitivity of SMA following shock.RESULTS: Ang-Ⅱ,PMA and KT-5823 improved the calcium sensitivity of SMA and made the cumulative dose-response curve of SMA to Ca~(2+) shift to the left,their Emax of Ca~(2+)(at 3?10~(-2) mol/L) was 0.630 g/mg,0.595 g/mg and 0.624 g/mg,respectively,which were all higher than that in shock control(0.377 g/mg)(P