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1.
Korean Journal of Nephrology ; : 352-361, 2001.
Article in Korean | WPRIM | ID: wpr-98007

ABSTRACT

High salt intake produces volume expansion and electrolyte imbalance in chronic renal failure and modifies the synthesis and secretion of atrial natriuretic peptide(ANP) to compensate the abnormalities in fluid and sodium handling. This study was performed to investigate the effect of high salt intake on modulation of cardiac and noncardiac ANP mRNA as well as plasma ANP levels in 5/6 subtotal nephrectomized (NPX) rats as a model of chronic renal failure. Adult male Sprague-Dawley rats were divided into sham and NPX rats. NPX rats were induced by 2/3 pole ligation and contralateral nephrectomy. Sham and NPX rats had access to normal chow with tap water for 8 weeks or normal chow with 0.45% NaCl solution(HS) for last 2 weeks. Plasma ANP levels were measured by radioimmunoassay. ANP mRNA from the right atrium, left ventricle, hypothalamus and kidney were analyzed by RT-PCR with 32P-dCTP at 8 weeks after surgical operation in both sham and NPX rats. Blood urea nitrogen(BUN) was measured to evaluate impaired renal function. Body weight, daily water intake, hemoglobin, red blood cell, hematocrit, arterial pressure and heart rate were also monitored. Arterial pressure in NPX+HS rat was significantly increased. Both percent increase of body weight and hematologic findings were decreased in NPX rats. Daily water intake was increased in NPX rats, especially in NPX+HS rat. BUN also increased in NPX rats. Plasma ANP concentration was significantly increased in sham+HS rat, but other significant increases were not shown in NPX rats. The levels of right atrial ANP mRNA represented the increasing trend like as plasma ANP. Left ventricular ANP mRNA was increased in sham+HS rat, while the level in NPX+HS rat was decreased comparing with that of sham+HS rat. Hypothalamic ANP mRNA was decreased in NPX+HS rat. In the kidney, the level of ANP mRNA in sham+HS rat was increased comparing with sham rat, but ANP synthesis in NPX+HS rat was significantly lower than in sham, sham+HS and in NPX rats. These findings represent that the high salt intake in NPX rat does not alter the plasma levels and cardiac synthesis of ANP but suppresses the renal ANP mRNA. The diminished renal ANP synthesis may attenuate the regulatory role of ANP system in the kidney and result in volume expansion and hypertension.


Subject(s)
Adult , Animals , Humans , Male , Rats , Arterial Pressure , Atrial Natriuretic Factor , Body Weight , Drinking , Erythrocytes , Heart Atria , Heart Rate , Heart Ventricles , Hematocrit , Hypertension , Hypothalamus , Kidney , Kidney Failure, Chronic , Ligation , Nephrectomy , Plasma , Radioimmunoassay , Rats, Sprague-Dawley , RNA, Messenger , Sodium , Urea , Water
2.
Korean Journal of Nephrology ; : 808-818, 2000.
Article in Korean | WPRIM | ID: wpr-9265

ABSTRACT

Chronic renal failure(CRF) may lead to fluid retention and electrolyte imbalance, and consequently increases the extracellular volume and blood pressure. These changes can trigger secretion and synthesis of atrial natriuretic peptide(ANP) as a compensatory regulator for increases in the glomerular filtration rate and excretion of water and sodium due to the reduced number of functional nephrons. ANP may exert important regulatory role on body fluid balance and blood pressure in CRF. We assessed changes in gene expression of atrial and extra-atrial ANP associated with progression of renal failure in subtotal nephrectomized rats. Adult male Sprague-Dawley rats were divided into sham and CRF rats. CRF rats were induced by 5/6 subtotal nephrectomy. We determined the plasma ANP level using by radioimmunoassay and the ANP mRNA from the right atrium, left ventricle, hypothalamus and kidney were measured by reverse transcription-polymerase chain reaction with 32P- dCTP at 8 wk in sham, and at 8 and 12 wk in CRF rats. Serum urea nitrogen(SUN) was also checked as an indicator of impaired renal function. SUN was significantly increased in CRF rats and the level was higher at CRF 12 wk rat than CRF 8 wk rat. Plasma concentration of ANP also increased in CRF rats compared with sham rat, but was not statistically significant. Altered patterns of ANP mRNA expression were different in each tissue. Right atrial and renal ANP mRNA expressions were slightly increased in CRF rats. Left ventricular ANP mRNA was significantly increased in CRF 8 wk rat compared with sham rat and maintained high at CRF 12 wk rat. However hypothalamic ANP mRNA expressions at CRF rats were decreased and the expression in CRF 12 wk was significantly lower than that at CRF 8 wk. SUN showed positive correlations with expression in left ventricular and renal ANP mRNA, but had a significant negative relationship with hypothalamic ANP mRNA. Plasma ANP concentration was positively correlated with the ANP mRNA expressions in both right atrium and kidney. The present study demonstrated that ANP mRNA in the right atrium, left ventricle, kidney and hypothalamus were differentially expressed upon CRF. This suggests that roles of the local ANP in these tissues are regulated by different mechanisms to compensate the fluid and electrolyte imbalance in rats with experimental chronic renal failure.


Subject(s)
Adult , Animals , Humans , Male , Rats , Atrial Natriuretic Factor , Blood Pressure , Body Fluids , Gene Expression , Glomerular Filtration Rate , Heart Atria , Heart Ventricles , Hypothalamus , Kidney , Kidney Failure, Chronic , Nephrectomy , Nephrons , Plasma , Radioimmunoassay , Rats, Sprague-Dawley , Renal Insufficiency , RNA, Messenger , Sodium , Solar System , Urea , Water
3.
Korean Journal of Aerospace and Environmental Medicine ; : 60-65, 1999.
Article in Korean | WPRIM | ID: wpr-177749

ABSTRACT

In the therapeutic or the nutritional aspects, Zn2+ has been used as a supplement in a variety of drugs. Most of divalent or trivalent cations affect ion channels in the cell membranes of various organs. In particular, Zn2+ has been regarded as a potassium (K+) channel blocker in the field of electrophysiology. ATP-sensitive K+ (KATP) channel, which is a kind of inward rectifier K+ channel, resides in the cell membrane of pancreatic beta cells and plays an important role in glucose-induced insulin secretion. The glucose increases intracellular ATP concentration, and this inhibits KATP channels. The inhibition of KATP channels activity depolarizes the cell, and subsequently, insulin is released by Ca2+ influx through the voltage- gated Ca2+ channels. Here, we demonstrate that KATP channels in the pancreatic beta cells are also the targets of extracellular Zn2+ blockade and its blockade is dependent on intracellular ATP concentration. This may be a compensatory mechanism preventing the oversecretion of insulin from the Pancreatic beta cells triggered by Zn2+ intake in a physiologically fasting condition.


Subject(s)
Adenosine Triphosphate , Cations , Cell Membrane , Electrophysiology , Fasting , Glucose , Insulin , Insulin-Secreting Cells , Ion Channels , KATP Channels , Potassium , Potassium Channels, Inwardly Rectifying
4.
Korean Journal of Aerospace and Environmental Medicine ; : 192-197, 1999.
Article in Korean | WPRIM | ID: wpr-157412

ABSTRACT

Brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission among the hippocampal neurons in the resting state. This mechanism may be due to the phosphorylation of NMDA receptors through its Trkb receptors on the postsynaptic neuron. In contrast, BDNF also has a suppressing effect on the synaptic transmission via non-NMDA receptors. The activities of non-NMDA receptors are known to modulate the NMDA receptors activities. This study was to investigate, using patch clamp technique, whether the BDNF increases or decreases the glutamate-induced synaptic transmission in which glutamate acts on both NMDA- and non-NMDA receptors. When a postsynaptic neuron was previously excited by a large amount of glutamate, BDNF decreased the synaptic transmission induced by subsequently-applied glutamate. However, when the signal entered into a postsynaptic neuron was blocked by the application of tetrodotoxin, BDNF increased the glutamate-induced responses. These results show that BDNF plays a role in a protection of the neurons against hazardous or uncontrolled activation of glutamate receptors and in an accentuation of the synaptic response when the signal is inevitably diminished.


Subject(s)
Brain-Derived Neurotrophic Factor , Glutamic Acid , Neurons , Phosphorylation , Receptor, trkB , Receptors, Glutamate , Receptors, N-Methyl-D-Aspartate , Synaptic Transmission , Tetrodotoxin
5.
Korean Journal of Aerospace and Environmental Medicine ; : 198-206, 1999.
Article in Korean | WPRIM | ID: wpr-157411

ABSTRACT

Kainate is known as a neurotoxin acting on the glutamate receptors in the central nervous system (CNS). Glutamate acts an excitatory neurotransmitter at physiological concentration but has a neurotoxic effect in excess amount. BDNF (brain-derived neurotrophic factor) has been reported to have a protective effect against the cellular toxicity and to plays an important role in neuronal survival and differentiation in peripheral nervous system. However, the functional mechanism of BDNF in CNS is unclear. This study was performed to examine the protective effect of BDNF in kainate-induced neurotoxicity and to observe the relation between BDNF mRNA expression and increasing pathways of intracellular Ca2+ concentration. Cultured hippocampal neurons were prepared from 17-18 day embryonic rats and used at the 7th day after neuronal culture. The amounts of BDNF mRNA were measured by reverse transcription polymerase chain reaction after the treatment of several glutamate receptor agonists: glutamate, kainate, -amino-3-hydroxyl-4-isoxazolepropionic acid, N-methyl-D-aspartate. Kainate showed the most prominent effect in an increase of BDNF mRNA expression among the glutamate receptor agonists. The maximal increase of BDNF mRNA expression was obtained in 50 M kainate at 3 hr after the treatment. Adding BDNF to kainate containing cultured hippocampal neurons diminished the increasing level of lactic dehydrogenase according to the single treatment of kainate. In the experiment to evaluate the Ca2+ influx pathways related in BDNF mRNA expression, nifedipine (10 M), a voltage-dependent Ca2+ channel blocker, decreased the both kainate (50 M) and KCl (50 mM) induced BDNF mRNA expressions by 18.4% and 35.0%, respectively. Ryanodine (10 M), a blocker of intracellular release from Ca2+ storage, however, did not show any effect in the both kainate- and KCl-treated neurons.These results suggest that BDNF has a protecting effect against the kainate-induced neurotoxicity in cultured rat hippocampal neurons, and its expression is more related with the Ca2+ influx through the voltage-dependent Ca2+ channels than the release from intracellular Ca2+ storage.


Subject(s)
Animals , Rats , Brain-Derived Neurotrophic Factor , Calcium , Central Nervous System , Glutamic Acid , Kainic Acid , N-Methylaspartate , Neurons , Neurotransmitter Agents , Nifedipine , Oxidoreductases , Peripheral Nervous System , Polymerase Chain Reaction , Receptors, Glutamate , Reverse Transcription , RNA, Messenger , Ryanodine
6.
Korean Journal of Aerospace and Environmental Medicine ; : 302-312, 1999.
Article in Korean | WPRIM | ID: wpr-46311

ABSTRACT

GABA (-aminobutyric acid) is one of the important neurotransmitters in the central nervous system of mammals and its action is variable according to the maturation phases of neurons. The neurons of early cultural days (less than 7 days) have been used for a developing neuronal model, while the neurons of later days (over 3 weeks) used for a mature model. This study was performed to investigate the electrophysiological property of GABAergic synapses in the hippocampal neurons cultured for 10 to 14 days which are considered to be transitional period between the developing and the mature phases. Membrane potential was depolarized and a inward transmembrane current was induced by 20 M GABA infusion. Frequency and amplitude of spontaneous postsynaptic currents (PSCs) were inhibited during the GABA infusion, but decay time constant was not affected significantly. In most hippocampal neurons, no GABAergic PSCs were observed during the administration of 0.5 M TTX, 50 M APV and 10 M CNQX. In the neurons counting 25% approximately, however, small persisted PSCs showed the existence of GABAergic synapses which were blocked by 10 M bicuculine. As the functional property of isolated GABAergic synapses, amplitude of GABAergic PSCs were diminished, and decay time constants and rising times were prolonged during the 20 M GABA infusion in all recorded neurons. In conclusion, approximately 25% of the hippocmpal neurons cultured 10 to 14 days used GABA as well as glutamate as a neurotransmitter. It seems that the GABAergic synapses composed of functionally homogenous GABAA receptors act as inhibitory modulator of the excitatory signal transmission.


Subject(s)
Animals , Rats , 6-Cyano-7-nitroquinoxaline-2,3-dione , Central Nervous System , gamma-Aminobutyric Acid , Glutamic Acid , Mammals , Membrane Potentials , Neurons , Neurotransmitter Agents , Synapses , Synaptic Potentials
7.
Korean Journal of Aerospace and Environmental Medicine ; : 71-80, 1997.
Article in Korean | WPRIM | ID: wpr-223378

ABSTRACT

The aim of this study was to determine the adaptation of atrial natriuretic peptide(ANP) to simulated weightlessness. The level of immunoreactive plasma ANP level and the expression of right atrial ANP mRNA were assessed in male Sparague-Dawley rats during 2 weeks of head-down suspension(HDS) The rats were placed in a -45 degrees anti-orthostatic position. The plasma ANP level was investigated by radioimmunoassay and ANP mRNA was expressed by Northern blot analysis. The changes in daily water intake, body weight and arterial hematocrit did not show the statistical significances during HDS. The plasma ANP level slightly increased after 1 day of HDS, the response was transient and then decreased below the control levels. The expression of the ANP mRNA increased after 1 day, the peak value occurred at 3 days of HDS and thereafter ANP mRNA showed the similar patterns compared to the changes of plasma level. On the basis of these findings, we conclude that the initial adaptation of ANP to increased control blood volume in rats occurs between 3 and 7 days of HDS, and the ANP acts an important role during regulatory process to central hypervolemia at both synthetic and secretory levels within the early stage of HDS.


Subject(s)
Animals , Humans , Male , Rats , Atrial Natriuretic Factor , Blood Volume , Blotting, Northern , Body Weight , Drinking , Hematocrit , Plasma , Radioimmunoassay , RNA, Messenger , Weightlessness
8.
Korean Journal of Obstetrics and Gynecology ; : 388-392, 1992.
Article in Korean | WPRIM | ID: wpr-82557

ABSTRACT

No abstract available.


Subject(s)
Female , Humans , Menstrual Cycle
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