1.Potassium channels and the modulators in vascular smooth muscle cells
Yuge JIANG ; Hai WANG ;
Chinese Pharmacological Bulletin 1986;0(05):-
It is well documented that vascular tone is the key determinant of blood vessel resistance and blood flow. But vascular tone could be regulated by modulating the activity of potassium channel directly. Potassium channel openers promote vasodilation by inhibiting the activity of voltage dependent calcium channels and reducing Ca 2+ influx. In this case, inhibition results from membrane hyperpolarisation, which arises due to the stimulation of K + efflux through smooth muscle K + channels. While K + channels are blocked, vasoconstriction could be observed as a result of membrane depolarization, which opens voltage dependent calcium channels. The influx of Ca 2+ can promote smooth muscle contraction by making myosin light chain phosphorylation and arising thick myofilament and thin myofilament relative movements. In this article, the gene structure, current character, Pharmacological and physiological effects of the four subtypes potassium channels are reviewed.
2.Effects of propofol on potassium currents in pulmonary artery smooth muscles of rats
Yuge JIANG ; Longhe XU ; Hong ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(07):-
AIM:To investigate the effects of propofol on potassium currents in pulmonary artery smooth muscle cells of normotensive and hypertensive rats. METHODS: The effects of propofol on potassium currents in smooth muscle cells derived from normotensive and hypertensive rats pulmonary arteries were observed by patch clamp technique (whole cell recording) after application of the drug in the bath. RESULTS: The potassium current-voltage curves (I-V curves) of smooth muscle cells derived from normotensive and pulmonary hypertensive rats pulmonary arteries were up-ward shifted by propofol (50, 100 ?mol/L). Compared with control group, within 5 minutes after application of the drug, the current amplitude could increase to (121?11)%, (113?5)% (P
3.Effects of agmatine on neuronal nitric oxide synthase in hippocampus of morphine withdrawal rats
Aiguo WANG ; Yuge JIANG ; Longhe XU
Chinese Journal of Tissue Engineering Research 2006;10(2):178-180
BACKGROUND: Agmatine can enhance the analgesic effect of morphine,and antagonize the tolerant and dependent effect of morphine.OBJECTIVE: To observe the effects of injecting agmatine on the neuronal nitric oxide synthase (nNOS) in hippocampus of morphine withdrawal rats.DESIGN: A randomized controlled experimental study.SETTING: Department of Anesthesiology, the General Hospital of Chinese PLA.MATERIALS: All the experiments were carried out in the Department of anesthesiology, the General Hospital of Chinese PLA between April and July 2004. Eighteen healthy SD rats were randomly divided into saline control group (n=6), morphine group (n=6) and agmatine-treated group (n=6).METHODS: The rats in the saline control group were treated with subcutaneous injection of physiological saline (10 mg/kg), those in the morphine group were treated with 5-day preconditioning, subcutaneous injection of morphine of 10, 20, 30, 40 and 50 mg/kg respectively, twice a day, and those in the agmatine-treated group were treated with subcutaneous injection of agmatine (10 mg/kg) at 30 minutes before morphine was given, but at 6 hours later, before morphine was given for the last time, the rats in the morphine group and agmatine treated group were also given intraperitoneal injection of naloxone (5 mg/kg) to induce morphine withdrawal symptoms.The number of times of the morphine withdrawal symptoms (including physical signs of trembling like a wet dog, chewing, irrigating, drooling, diarrhoea, etc.) were recorded within 1 hour, and the reduction of body mass was calculated according to the different value of body mass before and after the withdrawal symptoms induced by naloxone. The rats were killed under anesthesia after praxiological detection, and then hippocampus was taken out and made into frozen sections, and the nNOS was detected with immunohistochemical staining. The CMIAS systemwas applied for imaging analysis, and the average value of the integral absorbance (A) values in 5visual sights for each section was taken as the integral A value of positive neuron.MAIN OUTCOME MEASURES: ① The detected results of morphine withdrawal symptoms in each group; ② The changes of the nNOS expressions in hippocampus of rats in each group.RESULTS: All the 18 rats were involved in the analysis of results. ① The detected results of morphine withdrawal symptoms in each group: The withdrawal symptoms of trembling like a wet dog, chewing, irrigating, drooling,diarrhoea and reduction of body mass in the agmatine treated group were all obviously lower than those in the morphine group [(2.0±1.3), (5.0±1.1);(0.3±0.4), (1.8±0.7); (3.2±1.2), (6.8±3.1); (0.2±0.4), (1.2±0.9); (2.7±2.1),(6.7±2.1); (6.0±3.0), (12.8±2.7) times, P < 0.01], and close to those in the saline control group (P > 0.05). ② The changes of the nNOS expressions in hippocampus of rats in each group: The positive neurons of nNOS in hippocampus mainly distributed in CA1 region, the cytoplasm was stained buffy, and the round nuclei were stained pale purple by haematine. The immunofluorescent A value of positive neuron in the agmatine-treated group was significantly decreased as compared with that in the morphine group (24.32±8.31, 50.82±15.13, P< 0.01), and almost the same as that in the saline control group (24.32±8.31, 15.24±1.88, P > 0.05).CONCLUSION: Agmatine can inhibit the morphine withdrawal syndrome and decrease the expression of nNOS in hippocampus CA1 region of morphine-withdrawal rats. Hippocampal nitric oxide pathway takes part in the inhibitory effect of agmatine on morphine withdrawal syndrome.
4.Comparison of blocking effect of ropivacaine and bupivacaine on sodium channels of rat dosal root ganglia
Longhe XU ; Yuge JIANG ; Zeguo FENG ; Hong ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2002;0(05):-
AIM: To compare the blocking effect of ropivacaine and bupivacaine on sodium channels of rat dosal root ganglia(DRG) using whole cell recording technique. METHODS: Rat DRG neurons were enzymatically isolated , tetrodotoxin-sensitive(TTX-s) and tetrodotoxin-resistant (TTX-r) sodium currents of DRG were recorded by whole cell recording.Drugs were given in bath solution.The concentrations of ropivacaine were 10,30,100, 1 000 ?mol?L~ -1 and bupivacaine were 10,30,100,300 ?mol?L~ -1 . The recording number in each dose group was six. RESULTS: CsCl in extracellular fluid and TEA in intracellular fluid were used to block the potassium channels. Sodium currents were recorded when the holding potential was - 70 mV and a serials of pulse with step 10 mV and duration 70 ms was given.TTX-s sodium channel was recorded in 80.1 % large DRG cells and TTX-r sodium channel was recorded in 92.4 % medium and small DRG cells,of which 56.3 % cells had no response to 1 ?mol?L~ -1 TTX. The half-maximal blocking concentrations of ropivacaine on TTX-r sodium channel was 65.7 ? 6.1 ?mol?L~ -1 , which was much lower than that on TTX-s sodium channel 246.8 ? 11.2 ?mol?L~ -1 (P 0.05 ). CONCLUSION: Ropivacaine preferentially blocks TTX-r sodium channel.Selective blocking of TTX-r and TTX-s sodium channel was one of the reasons of seperation of sensation and motion when it is used in epidural anesthesia.
5.Compare effects of total intravenous anesthesia and balanced anesthesia on stress response on suspensive laryngoscope vocal cords surgery
Yuanyuan MAN ; Yuge JIANG ; Longhe XU ; Hong ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2002;0(05):-
AIM: To compare the effects of total intravenous anesthesia and balanced anesthesia on stress response on suspensive laryngoscope vocal cords surgery. METHODS: Thirty patients undergone microlaryngeal surgery were randomly divided into two groups(n=15). Analgesia and amnesia slow induction was used in all patiens with nosal incubation. During maintenance of anesthesia, propofol, remifentanil and scopolamine were used in total intravenous anesthesia group(group TIVA); fentanyl, scopolamine and isoflurane were used in balanced anesthesia group(group BAL). Record the data of each group,including base data, after induction, end of tracheal intubation,3 min after intubation, setting the suspensive laryngosopy, 3 min after setting the suspensive laryngosopy, removing the trachea, MAP, HR of each time, the time of recovery. The blood concentrations of epinephrine (E), noradrenalin(NE),cortisol,IL-6 were measured at each time point of base data, end of tracheal intubation, setting the suspensive laryngosopy, 3 min after setting the suspensive laryngosopy. RESULTS: There is no significant difference of HR, MAP, blood concentration of E,NE, cortisol, IL-6 at end of tracheal intubation compared with base data. AT setting the suspensive laryngosopy,3 min after setting the suspensive laryngosopy, HR, MAP, blood concentrations of E, NE, cortisol, IL-6 in group BAL were all higher than that of base data,and were also higher than group TIVA at the same time. The recovery time of group TIVA was shorter than that of group BAL. CONCLUSION: Analgesia and amnesia slow induction with nosal intubaion and maintenance with remifentanil, propofol can inhibit sudden change of hemodynamics and stress response of intubation and setting the suspensive laryngoscope, with quicker recovery .It is an ideal anesthesia method for suspensive laryngoscope vocal cords surgery.
6.Effects of Ropivacaine and Bupivacaine on glutamate-evoked currents in cultured rat hippocampal neurons
Yuge JIANG ; Weidong MI ; Longhe XU ; Hong ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 1999;0(04):-
AIM: To observe and compare the effects of Ropivacaine and Bupivacaine on glutamate-evoked currents in cultured rat hippocampus neurons.METHODS: Rat hippocampal neurons were dissociated and cultured.Glutamate-evoked currents were recorded by whole cell patch clamp recording.Effects of Ropivacaine and Bupivacaine on glutamate-evoked currents were observed.Drugs were given by pressure ejection or applicated in the bath.RESULTS: Glutamate(100(mmol?L~(-1))) can activate inward currents in cultured rat hippocampus neurons and this currents could be locked by non-NMDA antagonists DNQX.At concentrations of 10,50,100(mmol?L~(-1)),both Bupivacaine and Ropivacaine could obviously decrease glutamate-evoked currents in cultured rat hippocampus neurons.At higher concentration of 50 and 100(mmol?L~(-1)),the reduced amplitude of glutamate-evoked currents by Ropivacaine was larger than that of by Bupivacaine(P
7.Effects of iptakalim hydrochloride on potassium currents in artery smooth muscles
Yuge JIANG ; Xiaofeng YIN ; Wenyu CUI ; Hai WANG
Chinese Pharmacological Bulletin 1986;0(05):-
AIM To investigate the effects of the novel antihypertensive drug iptakalim hydrochloride on potassium currents in artery smooth muscle cells. METHODS The effects of iptakalim hydrochloride on potassium currents in smooth muscle cells derived from rat pulmonary arteries were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. RESULTS The potassium current-voltage curves ( I-U curves) of smooth muscle cells derived from normotensive rat pulmonary arteries were up-ward shifted by iptakalim hydrochloride(0.1,1,10 and 100 ?mol?L -1 ). Within 5 minutes after application of the drug, the current amplitude could increase to[(118.6?15.9)%, P
8.LINC00926 promotes pyroptosis of hypoxia-induced human umbilical vein vascular endothelial cells by recruiting ELAVL1.
Yong JIANG ; Wenting GE ; Ying ZHAO ; Yuge WU ; Yiming HUO ; Lanting PAN ; Shuang CAO
Journal of Southern Medical University 2023;43(5):807-814
OBJECTIVE:
To investigate the regulatory role of the long non-coding RNA LINC00926 in pyroptosis of hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) and explore the molecular mechanism.
METHODS:
HUVECs were transfected with a LINC00926-overexpressing plasmid (OE-LINC00926), a siRNA targeting ELAVL1, or both, followed by exposure to hypoxia (5% O2) or normoxia. The expression of LINC00926 and ELAVL1 in hypoxia-treated HUVECs was detected using real-time quantitative PCR (RT-qPCR) and Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8), and the levels of IL-1β in the cell cultures was determined with ELISA. The protein expression levels of pyroptosis-related proteins (caspase-1, cleaved caspase-1 and NLRP3) in the treated cells were analyzed using Western blotting, and the binding between LINC00926 and ELAVL1 was verified with RNA immunoprecipitation (RIP) assay.
RESULTS:
Exposure to hypoxia obviously up-regulated the mRNA expression of LINC00926 and the protein expression of ELAVL1 in HUVECs, but did not affect the mRNA expression of ELAVL1. LINC00926 overexpression in the cells significantly inhibited cell proliferation, increased IL-1β level and enhanced the expressions of pyroptosis-related proteins (all P < 0.05). LINC00926 overexpression further up-regulated the protein expression of ELAVL1 in hypoxia-exposed HUVECs. The results of RIP assay confirmed the binding between LINC00926 and ELAVL1. ELAVL1 knockdown significantly decreased IL-1β level and the expressions of pyroptosis-related proteins in hypoxia-exposed HUVECs (P < 0.05), while LINC00926 overexpression partially reversed the effects of ELAVL1 knockdown.
CONCLUSION
LINC00926 promotes pyroptosis of hypoxia-induced HUVECs by recruiting ELAVL1.
Humans
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Caspase 1
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ELAV-Like Protein 1
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Human Umbilical Vein Endothelial Cells
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Pyroptosis
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RNA, Messenger
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RNA, Long Noncoding/genetics*
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Cell Hypoxia