大鼠饮盐行为的个体发生的研究

研究不同性别的发育期大鼠饮盐行为的发生年龄及其与大鼠血浆醛固酮（ＡＬＤＯ）水平之间的关系,为研究高血压病提供基础资料。方法：用自控泵经口腔导管给大鼠灌注３％盐水,记录大鼠的饮盐水量。结果：禁盐能引起１３ｄ龄及１３ｄ龄以上大鼠的饮盐行为。而不能引出１３ｄ龄以下幼鼠的饮盐行为。幼鼠的饮盐行为无显著的性别差异。这与禁盐引起各年龄组大鼠的血浆ＡＬＤＯ水平都显著升高的现象不一致。结论：大鼠饮盐行为的发生与大鼠的年龄有关,与大鼠脑的发育,特别是与大鼠的饮盐中枢的发育及完善有关。     

Sodium channel blockade enhances dispersion of the cardiac action potential duration

Summary The goal of this study was to elucidate the causes why the proarrhythmic activity of sodium channel blocking drugs is enhanced during the post-infarction period. Therefore, we studied the effects of a reduction in sodium conductance on the action potential duration and its dispersion in a simulated array of 1600 ventricular myocytes. Cardiac tissue is known to possess anisotropic properties with regard to the intercellular electrical resistance (R). Infarction as well as aging causes deposition of collagen in the cardiac tissue, thereby inducing zones of high electrical resistance leading to a non-uniform anisotropy (Spach et al., Circ Res 62811, 1988). For our study an array of 40*40 ventricular myocytes was simulated using Beeler-Reuter-algorithms. Physical tissue properties were assumed to be either a) uniform anisotropic (i.e., all longitudinal R=5000 cm, all transversal R=20000 cm; UA) or b) non-uniform anisotropic (i.e., transversal R for the inner 10*10 cells was set to 10¹⁰ cm; NUA). Mean action potential duration (APD) was increased under UA (287 ms, dispersion: 0,8 ms) when compared to NUA (285 ms, disp.: 3,2 ms). Assuming a 25% decrease in sodium conductance, we found the total activation time (TAT) to be increased (from 99 to 139 ms), indicating slowing of conduction, APD to be shortened (from 287 to 259 ms), and the APD-dispersion to be increased (from 0.8 to 29 ms) in UA. These changes were more pronounced in the case of NUA: increase in TAT from 103 to 150 ms, APD-shortening from 285 to 214 ms and a marked increase in APD-Dispersion from 3.2 to 53 ms). From these results it is concluded that a) the effects of a reduced sodium conductance are more pronounced in NUA tissue, and b) that the resulting increase in dispersion may provoke arrhythmia by local differences in APD.This may be one of the mechanisms underlying the increased proarrhythmic risk of class I antiarrhythmic drugs in the postinfarction period.     

Noradrenaline transport by rat heart sympathetic nerves: A re-examination of the role of sodium ions

Summary The effect of sodium ion on ³H-(–)-noradrenaline (0.0875 to 0.5 M) transport by rat heart atrial hemi-appendages incubated in vitro has been studied, and the following observations made: a) When sodium was omitted (choline and lithium substitution) there was no evidence for active noradrenaline transport, and only a component that did not show saturation kinetics up to 1 M noradrenaline, remained. b) Omission of sodium or addition of 4×10^–5 M desipramine inhibited noradrenaline transport to exactly the same extent, and their effects were not additive. Alprenolol did not reduce this sodium-independent transport, but tropolone lowered it somewhat. c) No evidence for corticosterone-sensitive noradrenaline transport (uptake-2) was found in this preparation at the low amine concentrations used. d) In control medium, the kinetic parameters of transport were: K _m: 0.59 ± 0.063 M and V _max: 2.44 ± 0.43 (pmoles/mg protein/min). With 26 mM sodium and the rest substituted by choline, K _m:2.26 ± 0.70 M (P0.001) and V _max: 2.74 ± 0.43 (pmoles/mg protein/min) (not significant). Also with 26 mM sodium, but with sucrose substitution, K _m: 0.76 ± 0.13 M (N.S.) and V _max: 1.06 ± 0.13 (pmol/mg/min) (P<0.05). Such results indicate that sodium only modifies the affinity of the transport system for noradrenaline, without changing V _max, and that changes in the latter are only a consequence of a reduction of the ionic strength. e) When noradrenaline transport was studied at different concentrations of external sodium, at constant ionic strength and with precautions to minimize the noradrenaline-releasing effect of low sodium, it was found that the data could be best represented by two hyperbolas placed in series. This suggests that the noradrenaline carrier has two sites for sodium, that do not interact with each other. When the same experiments were repeated in the absence of chloride, it was found that the noradrenaline transport system had lost virtually all its affinity for sodium. f) The effect of prolonged tissue incubation in the absence of sodium was found to produce a relatively small inactivation of noradrenaline transport. Such phenomenon was enhanced by raising the calcium concentration to 2 mM.     

Symptomatic hyponatraemia due to inappropriate antidiuretic hormone secretion following minor surgery

A rare case of the syndrome of inappropriate antidiuretic hormone secretion occurring after minor surgery is presented. A ten-year-old, previously healthy boy underwent general anaesthesia for detorsion and right orchiopexy. Throughout the operations, which lasted for one hour, he received 120 ml Ringer's lactate solution. The immediate postoperative period was uneventful. Twenty-two hours postoperatively he was found unconscious with generalized tonic-clonic seizures. Simultaneously obtained serum sodium concentration (121 mEq.L-1) serum osmolarity (265 mEq.L-1), urine sodium concentration (87 mEq.L-1) and urine osmolarity (525 mEq.L-1) suggested inappropriate antidiuretic hormone secretion which was confirmed by an elevated serum arginine-vasopressin (AVP) level of 14.5 pcg.ml-1 (normal 1-5 pcg.ml-1) measured by radioimmune assay. He was treated with a single iv dose of 30 mg furosemide and fluid restriction, which produced a gradual increase of his serum sodium concentration to normal within two days. He was well during the remainder of his hospitalization.     

Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat

Summary The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml ·kg^–1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure.In healthy rats saralasin (6 g·kg^–1·min^–1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng·kg^–1·min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.Supported by Deutsche Forschungsgemeinschaft     

Enhancement of persistent Na+ current by sea anemone toxin (ATX II) exerts dual action on hippocampal excitability

We used anemone toxin II (ATX II) to study how a selective enhancement of persistent Na+ current (INaP) would affect the excitability of CA1 pyramidal neurons in the hippocampal slice. In whole-cell recordings from CA1 cell somata, local application of ATX II (10 microM) into the stratum pyramidale invariably depolarized the neurons and produced sustained burst discharges with depolarizing plateau potentials of variable amplitude and length. However, the strong excitatory action of ATX II, observed on the single cell level, was not mirrored in field potential recordings from the same hippocampal subfield. The amplitude of the electrically evoked population spike declined, reflecting the decreased availability of fast Na+ channels, and the intracellulary recorded burst discharges were not detected by the field electrode. The lacking synchronization of cellular bursting activity was seen during both local and bath application of ATX II, suggesting that the toxin, in addition to promoting burst discharges of individual neurons, simultaneously dampens network excitability. In fact, ATX II reduced afferent fibre volleys (reflecting axonal excitability) and field excitatory postsynaptic potentials (EPSPs) in a similar fashion. As the expression of different Na+ channel subtypes appears to be compartmentalized within hippocampal neurons, we propose that point mutations leading to pathologically enhanced INaP might exert quite opposite effects, depending on the type and location of the Na+ channel affected. Whereas alterations of somatodendritic Na+ channels would give rise to bursting activity, alterations of axonal Na+ channels would primarily decrease network excitability.     

Transport and uptake characteristics of a new derivative of berberine(CPU-86017) by human intestinal epithelial cell line: Caco-2

AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13α-tetrahydroberberine chloride, CTHB]}, a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5 mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100 μmol/L and low pH (pH=6.0) induced a reversible d     

Puerarin blocks Na~+ current in rat ventricular myocytes

AIM: To study the effect of puerarin (Pue) on Na~+ channel in rat ventricular myocytes. METHODS: Whole-cell patch-clamp technique was applied on isolated cardiomyocytes from rats. RESULTS: Pue inhibited cardiac I_(Na) in a positive rate-dependent and dose-dependent manner, with an IC_(50) of 349 μmol/L. The kinetics of blockage of cardiac sodium channel by Pue resembled the ClassIa/Ic of antiarrhythmic agents. Pue 300 μmol/L did not alter the shape of the I-V curve of I_(Na), but markedly shifted the steady-state inactivation curve of I_(Na) towards more negative potential by 15.9 mV, and postponed the recovery of I_(Na) inactivation state from (21.9±1.6) ms to (54.4±3.4) ms (P<0.01 ). It demonstrated that the steady state of inactivation was affected by Pue significantly. CONCLUSION: Pue protected ventricular myocytes against cardiac damage and arrhythmias by inhibiting recovery from inactivation of cardiac Na~+ channels.