Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensit...Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.展开更多
Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been ...Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.展开更多
Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the additio...Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.展开更多
Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blaza...Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.展开更多
Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in...Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks.Thirteen healthy New Zealand white rabbits were randomly selected as controls.After atherosclerosis induction,standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery.Contrast-enhanced ultrasound(CEUS)was performed at baseline and during intravenous injection of NE.The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.Results The serum nitric oxide(NO)level in atherosclerotic rabbits was higher than that in healthy rabbits(299.6±152 vs.136.5±49.5,P<0.001).The infusion of NE induced a significant increase in the systolic blood pressure(112±14 mmHg vs.84±9 mmHg,P=0.016)and a significant decrease in the enhanced intensity in renal cortex(17.78±2.07 dB vs.21.19±2.03 dB,P<0.001)and renal medulla(14.87±1.82 dB vs.17.14±1.89 dB,P<0.001)during CEUS.However,the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.Conclusion NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis,partly by reducing the serum NO level.展开更多
BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolizatio...BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolization.Provocative angiography is helpful in the detection of elusive bleeding.AIM We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies,as well as the role of norepinephrine(NE)in unmasking bleeding.METHODS We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years.All patients had a positive shock index and needed intensive care.RESULTS In three of four patients,angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization.CONCLUSION We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization.However,this statement must be confirmed in prospective studies.展开更多
We analyze the optical light curve data,obtained with the Zwicky Transient Facility(ZTF)survey,for 47 γ-ray blazars monitored by the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope(Fermi).These 47sou...We analyze the optical light curve data,obtained with the Zwicky Transient Facility(ZTF)survey,for 47 γ-ray blazars monitored by the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope(Fermi).These 47sources are selected because they are among the Fermi blazars with the largest optical variations in the ZTF data.Two color-magnitude variation patterns are seen in them,with one being redder-to-stable-when-brighter(RSWB;in 31 sources)and the other being stable when brighter(in 16 sources).The patterns fit with the results recently reported in several similar studies with different data.Moreover,we find that the colors in the stable state of the sources share similar values,for which(after being corrected for the Galactic extinction)most sources are in a range of 0.4–0.55.This feature could be intrinsic and may be applied in,for example,study of the intragalactic medium.We also determine the turning points for the sources showing the RSWB pattern,after which the color changes saturate and become stable.We find a correlation between optical fluxes and γ-ray fluxes at the turning points.The physical implications of the correlation remain to be investigated,probably better with a sample of high-qualityγ-ray flux measurements.展开更多
文摘Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.
文摘Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.
文摘Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.
文摘Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.
基金supported by grants from Health and Family Planning Commission Foundation of Hubei Province(No.WJ2017M080)the National Natural Science Foundation of China(No.81601507).
文摘Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks.Thirteen healthy New Zealand white rabbits were randomly selected as controls.After atherosclerosis induction,standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery.Contrast-enhanced ultrasound(CEUS)was performed at baseline and during intravenous injection of NE.The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.Results The serum nitric oxide(NO)level in atherosclerotic rabbits was higher than that in healthy rabbits(299.6±152 vs.136.5±49.5,P<0.001).The infusion of NE induced a significant increase in the systolic blood pressure(112±14 mmHg vs.84±9 mmHg,P=0.016)and a significant decrease in the enhanced intensity in renal cortex(17.78±2.07 dB vs.21.19±2.03 dB,P<0.001)and renal medulla(14.87±1.82 dB vs.17.14±1.89 dB,P<0.001)during CEUS.However,the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.Conclusion NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis,partly by reducing the serum NO level.
文摘BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolization.Provocative angiography is helpful in the detection of elusive bleeding.AIM We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies,as well as the role of norepinephrine(NE)in unmasking bleeding.METHODS We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years.All patients had a positive shock index and needed intensive care.RESULTS In three of four patients,angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization.CONCLUSION We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization.However,this statement must be confirmed in prospective studies.
基金supported by the National Science Foundation under Grant No.AST-2034437 and a collaboration including Caltech,IPACsupported by the Basic Research Program of Yunnan Province(No.202201AS070005)+2 种基金the National Natural Science Foundation of China(NSFC,grant No.12273033)the Original Innovation Program of the Chinese Academy of Sciences(E085021002)the support of the science research program for graduate students of Yunnan University(KC-23234629)。
文摘We analyze the optical light curve data,obtained with the Zwicky Transient Facility(ZTF)survey,for 47 γ-ray blazars monitored by the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope(Fermi).These 47sources are selected because they are among the Fermi blazars with the largest optical variations in the ZTF data.Two color-magnitude variation patterns are seen in them,with one being redder-to-stable-when-brighter(RSWB;in 31 sources)and the other being stable when brighter(in 16 sources).The patterns fit with the results recently reported in several similar studies with different data.Moreover,we find that the colors in the stable state of the sources share similar values,for which(after being corrected for the Galactic extinction)most sources are in a range of 0.4–0.55.This feature could be intrinsic and may be applied in,for example,study of the intragalactic medium.We also determine the turning points for the sources showing the RSWB pattern,after which the color changes saturate and become stable.We find a correlation between optical fluxes and γ-ray fluxes at the turning points.The physical implications of the correlation remain to be investigated,probably better with a sample of high-qualityγ-ray flux measurements.
