利钾尿肽和心钠素在自发性高血压大鼠肾内的降解代谢

利钾尿肽 (ｋａｌｉｕｒｅｔｉｃｐｅｐｔｉｄｅ ,ＫＰ)是近年发现的与心钠素 (ａｔｒｉａｌｎａｔｒｉｕｒｅｔｉｃｐｅｐｔｉｄｅ ,ＡＮＰ)源于同一前体的具有 2 0个氨基酸的生物活性多肽。它不仅具有和心钠素一样的利尿、舒张血管、抑制肾素一血管紧张素系统的作用 ,还具有抑制心肌Ｎａ -Ｋ ＡＴＰ酶的作用 ,在调节机体血压和高血压发病中有重要意义。我们最近的研究发现 ,自发性高血压大鼠 (ｓｐｏｎｔａｕｅｏｕｓｌｙｈｙｐｅｒｔｅｎｓｉｖｅｒａｔ,ＳＨＲ)循环血液内的ＫＰ水平显著高于正常对照组Ｗｉｓｔａｒ Ｋｙｏｔｏ大鼠 (Ｗ…     

小麦根质膜H^＋—ATPase的部分纯化

以小麦（ＴｒｉｔｉｃｕｍａｅｓｔｉｖｕｍＬ．）根为材料,采用不连续蔗糖密度梯度离心法制备高纯度质膜微囊。质膜经ＴｒｉｔｏｎＸ１００和ＫＣｌ处理后,再用Ｚｗｉｔｅｒｇｅｎｔ３１４增溶Ｈ＋ＡＴＰａｓｅ,最后用硫酸铵沉淀得到部分纯化的质膜Ｈ＋ＡＴＰａｓｅ。ＳＤＳＰＡＧＥ结果表明,经过上述步骤纯化,分子量为９４ｋＤ的膜蛋白组分得到富集;与质膜相比,其含量提高１５．７倍。部分纯化的质膜Ｈ＋ＡＴＰａｓｅ可以水解ＡＴＰ,受Ｋ＋刺激,并被Ｎ,Ｎ′ｄｉｃｙｃｌｏｈｅｘｙｌｃａｒｂｏｄｉｍｉｄｅ（ＤＣＣＤ）抑制;ＡＴＰ水解活力被Ｎａ３ＶＯ４抑制９５％,但不被ＮａＮ３、ＮａＮＯ３和Ｎａ２ＭｏＯ４抑制。     

TAD对大鼠肾缺血后肾组织Na~+、K~+-ATP酶活性的影响

选用大鼠右肾切除、左侧肾蒂夹闭６０ｍｉｎ继之再灌流不同时间动物模型,用光镜组化、电镜组化和计算机显微图像分析方法观察肾小管上皮Ｎａ＋、Ｋ＋┐ＡＴＰ酶活性的变化及ＴＡＤ（还原型谷胱甘肽）对它们的影响。结果显示：正常肾组织光镜下Ｎａ＋、Ｋ＋┐ＡＴＰ酶主要分布在髓质外带、髓袢升支粗段的肾小管上皮细胞;电镜下Ｎａ＋、Ｋ＋┐ＡＴＰ酶分布在细胞基部质膜内褶的胞浆面。６０ｍｉｎ肾缺血后再灌流１５ｍｉｎ、２４ｈ可致肾小管上皮Ｎａ＋、Ｋ＋┐ＡＴＰ酶活性呈进行性降低,给予自由基清除剂ＴＡＤ后,肾小管上皮Ｎａ＋、Ｋ＋┐ＡＴＰ酶活性损伤有所减轻。结果提示：自由基可能损害肾上管上皮Ｎａ＋、Ｋ＋┐ＡＴＰ酶活性,ＴＡＤ可能保护肾小管Ｎａ＋、Ｋ＋┐ＡＴＰ酶活性     

粉防己碱对大鼠心肌缺血再灌注时心肌ATP酶活性的影响

实验旨在观察在体大鼠短暂缺血后心肌膜ＡＴＰ酶活性的变化及粉防己碱（Ｔｅｔ）的作用。分离缺血１５ｍｉｎ、再灌注２ｈ后及在缺血再灌注前给Ｔｅｔ的大鼠心肌粗制质膜和内质网,测定质膜Ｎａ＋－Ｋ＋－ＡＴＰ酶和内质网Ｃａ２＋－ＡＴＰ酶活性。结果表明,心肌缺血１５ｍｉｎ后二酶活性均明显降低,分别为假结扎组的６３．６％和７２．６％（Ｐ＜０．０１）,再灌注后Ｎａ＋－Ｋ＋－ＡＴＰ酶活性有所恢复,再灌注３０ｍｉｎ时为假结扎组的７２．１％（Ｐ＜０．０１）,而Ｃａ２＋－ＡＴＰ酶活性则进一步下降,再灌注３０ｍｉｎ时为假结扎组的５０．４％（Ｐ＜０．０１）,再灌注后２ｈ二酶活性分别升高至假结扎组的８０．９％和６５．３％（Ｐ＜０．０１）。在缺血前２０ｍｉｎ分别给予Ｔｅｔ６４．２和９６．３μｍｏｌ／ｋｇ及硝苯啶（０．２３μｍｏｌ／ｋｇ）,能明显减少内质网Ｃａ２＋－ＡＴＰ酶活性的降低。结果提示心肌膜ＡＴＰ酶活性的降低可能参与了短暂心肌缺血所致再灌注损伤的发生机制,Ｔｅｔ可减少缺血和／或再灌注时内质网Ｃａ２＋－ＡＴＰ酶活性降低。     

游泳训练与大鼠骨骼肌细胞膜电位及Na6＋,K^＋—ATP酶活性之…

大鼠腓肠肌在１０ＨＺ电刺激持续收缩运动中,肌细胞膜电位表现为静息电位（ＲＰ）和复合动作电位（ＣＡＰ）幅值呈下降的趋势,且ＣＡＰ的时程展宽。经过９周的游泳训练后,训练组动物整体的运动耐力明显提高;在相同的持续收缩运动时间内,训练组的ＲＰ和ＣＡＰ的下降幅度明显小于对照组（Ｐ＜０．０５）;并发现训练组Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶活性明显提高（Ｐ＜０．０１）。结果提示,体力训练使肌细胞膜的３功能产生了适应性     

模拟失重对大鼠心肌力学与生物化学的影响

观察为期４周模拟失重对大鼠心肌收缩性能与收缩蛋白性质的影响,发现模拟失重大鼠左心室乳头肌等长收缩的力学特征发生下列变化：发展张力峰值降低２９％（Ｐ〈０．０１）;达到张力峰值的时间延长１０％（Ｐ〈０．０５）;舒张一半的时间缩短１１％,但未达到显著水平（Ｐ〉０．０５）。心肌力学参数的这些变化表明模拟失重使大鼠心肌收缩性能降低。进一步研究显示,模拟失重大鼠左室心肌肌原纤维Ｃａ＾２＋,Ｍｇ＾２＋－ＡＴＰ酶     

游泳训练与大鼠骨骼肌细胞膜电位及Na~＋，K~＋－ATP酶活性之间关系的探讨

大鼠腓肠肌在１０Ｈｚ电刺激持续收缩运动中,肌细胞膜电位表现为静息电位（ＲＰ）和复合动作电位（ＣＡＰ）幅值呈下降的趋势,且ＣＡＰ的时程展宽。经过９周的游泳训练后,训练组动物整体的运动耐力明显提高;在相同的持续收缩运动时间内,训练组的ＲＰ和ＣＡＰ的下降幅度明显小于对照组（Ｐ＜０．０５）;并发现训练组ＮＡａ￣＋,Ｋ￣＋－ＡＴＰ酶活性明显提高（Ｐ＜０．０１）。结果提示,体力训练使肌细胞膜的功能产生了适应性变化,提高了对运动的耐受能力。     

脓毒血症早晚期肝细胞核被膜NTPase活性及poly（A）^＋m …

目的和方法：在育肠结扎穿孔脓毒血症大鼠模型上,研究早晚期脓毒血症肝细胞核被膜核苷三磷酸酶（ＮＴＰａｅｓ）活性及ｐｏｌｙ（Ａ）＾＋ｍＲＮＡ核浆转运的变化。结果：脓毒血症早期ＮＴＰａｓｅ活性增加而晚期活性降低,即早期Ｖｍａｘ与对照组比增加６２％（ＡＴＰ,Ｐ〈０．０５）和１８％（ＧＴＰ,Ｐ〈０．０５）;晚期Ｖｍａｘ下降２６％（ＡＴＰ,Ｐ〈０．０５）和５６％（ＧＴＰ,Ｐ〈０．０５）。脓毒血症伏晚期ＮＴＰａ     

氟烷,七氟醚对缺血再灌注心肌功能和ATP酶活性的影响

心肌缺血再灌注过程中细胞内存在着严重的Ｃａ２＋、Ｎａ＋紊乱。Ｃａ２＋ＡＴＰ酶和Ｎａ＋,Ｋ＋ＡＴＰ酶在维持细胞内外离心平衡中起着重要作用。本文用大鼠离体心脏Ｌａｎｇｅｎｄｏｒｆ模型结合缺血前后心功能指标的变化,研究氟烷、七氟醚对缺血前、缺血期、复灌...     

大鼠海马神经元Na~ Ca~(2 )交换电流在低氧时的变化

目的：探讨在低氧性脑损伤发生过程中,Ｎａ＋Ｃａ２＋ 交换体在细胞内钙超载中的作用。方法：采用全细胞膜片钳方法,在急性分离海马神经元上观察低氧对Ｎａ＋Ｃａ２＋ 交换电流的电流电压（ＩＶ） 曲线的影响。结果：在整个膜电位水平,Ｎａ＋Ｃａ２＋ 交换电流幅值均不同程度的增加,在正膜电位水平呈现一显著的外向电流。１０ ｍＶ 时,电流幅值从（９２ ．８３ ±２０．８）ｐＡ上升到（１３０ ．６７ ±２６．８８）ｐＡ（ Ｐ＜０ ．０５） ,而在５０ ｍ Ｖ,其电流幅值从（－ ７４ ．６７ ±１１ ．８４）ｐＡ上升到（－ ５８ ．５±１０ ．７１）ｐＡ（Ｐ＜ ０ ．０５）。结论：低氧时Ｎａ＋Ｃａ２＋ 交换电流呈外向性,这种改变有利于低氧后通过Ｎａ＋Ｃａ２＋ 交换的外向转运方式排出细胞内钠,并交换钙进入细胞     

Ouabain-insensitive Na+-ATPase of proximal tubules is an effector for urodilatin and atrial natriuretic peptide

In the present paper we studied the effect of urodilatin and atrial natriuretic peptide (ANP) on the proximal tubule Na+-ATPase and (Na+K+)ATPase activities. Urodilatin and ANP inhibit the Na+-ATPase activity but not the (Na+K+)ATPase activity. Maximal effect was observed at a concentration of 10(-11) M for both peptides. In this condition, the enzyme activity decreases from 10.8 +/- 1.6 (control) to 5.7 +/- 0.9 or 6.1 +/- 0.7 nmol Pi mg(-1) min(-1) in the presence of urodilatin or ANP, respectively. This effect was completely reversed by 10(-6) M LY83583, a guanylyl cyclase inhibitor, and mimicked by 10 nM cGMP. Furthermore, both ANP and urodilatin increase cGMP production by 33% and 49%, respectively. This is the first demonstration that it was shown that urodilatin and ANP directly modulate primary active sodium transport in the proximal tubule. The data obtained indicate that this effect is mediated by the activation of the NPR-A/guanylate cyclase/cGMP pathway.     

人胚心肌纤维中心房特殊颗粒的分布及心钠素的免疫组化研究

收集胚胎标本共24例（经临床证实孕妇无心血管疾病）,用透射电镜观察各胎龄心脏各部位心肌纤维中心特殊颗粒（ASG）分布及含量变化,同时结合免疫组织化学技术对心脏各部位心肌纤维内心钠素的表达进行研究。结果表明,胚第5周时,心肌纤维便有ASG出现,随着胎龄的增长,心房与心耳的颗粒数量逐渐增多。而心室的颗粒数量却逐渐减少,在同一胎龄,心房内的颗粒数量多于心室,心耳ASG多于心房,免疫组织化学的研究结果表明,胚第7周时,心房与心耳内可出现心钠素样免疫反应阳性的心肌细胞,其阳性反应的变化规律与ASG的变化规律一致。心室中未发现阳性反应。     

Mechanics of left ventricular relaxation, early diastolic lengthening, and suction investigated in a mathematical model

We investigated the determinants of ventricular early diastolic lengthening and mechanics of suction using a mathematical model of the left ventricle (LV). The model was based on a force balance between the force represented by LV pressure (LVP) and active and passive myocardial forces. The predicted lengthening velocity (e') from the model agreed well with measurements from 10 dogs during 5 different interventions (R = 0.69, P < 0.001). The model showed that e' was increased when relaxation rate and systolic shortening increased, when passive stiffness was decreased, and when the rate of fall of LVP during early filling was decreased relative to the rate of fall of active stress. We first defined suction as the work the myocardium performed to pull blood into the ventricle. This occurred when contractile active forces decayed below and became weaker than restoring forces, producing a negative LVP. An alternative definition of suction is filling during falling pressure, commonly believed to be caused by release of restoring forces. However, the model showed that this phenomenon also occurred when there had been no systolic compression below unstressed length and therefore in the absence of restoring forces. In conclusion, relaxation rate, LVP, systolic shortening, and passive stiffness were all independent determinants of e'. The model generated a suction effect seen as lengthening occurring during falling pressure. However, this was not equivalent with the myocardium performing pulling work on the blood, which was performed only when restoring forces were higher than remaining active fiber force, corresponding to a negative transmural pressure.     

Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs

The effects on myocardial function and loading conditions of clinically relevant doses of the natriuretic peptides (NP) have not been established. The actions of single doses (100 ng x kg(-1) x min(-1) iv over 30 min) of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) were studied in conscious normal dogs and in dogs with pacing-induced heart failure. All three NP reduced end-diastolic pressure in normal dogs, and ANP and BNP reduced end-diastolic volume. In heart failure ANP and BNP reduced EDP, and ANP reduced EDV. Arterial elastance was unchanged in normal dogs and in dogs with heart failure. ANP increased end-systolic elastance (E(es)) in normal dogs, whereas BNP tended to increase E(es) (P = 0.06). In dogs with heart failure, no inotropic effect was seen. In normal dogs, all NP reduced the time constant of isovolumic relaxation (tau), and ANP and BNP reduced tau in dogs with heart failure. Increases in plasma cGMP in dogs with heart failure were blunted. The NP reduced preload and enhanced systolic and diastolic function in normal dogs. Effects of ANP and BNP on preload and diastolic function were maintained in heart failure. Lack of negative inotropic effects in heart failure supports the validity of the NP as therapeutic agents.     

ANP but not BNP reflects early left diastolic dysfunction in type 1 diabetics with myocardial dysinnervation.

OBJECTIVE: We investigated whether plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) reflect impaired diastolic relaxation or its improvement after ACE inhibition. METHODS: 7 long-term Type 1 diabetic patients with normal systolic but impaired diastolic function and with sympathetic myocardial dysinnervation and 10 controls were included. Exercise tolerance and maximal O 2 uptake were evaluated by bicycle exercise prior to the study. ANP, BNP and norepinephrine/epinephrine (NE/E) were determined at baseline and at 80 % .VO2 max workload and after recovery, before and following 12 weeks of treatment with fosinopril (10 mg/d). RESULTS: Isovolumetric relaxation time (IVRT) and A/E wave ratio were increased by 26.7 +/- 11.5 % and 54.4 +/- 26.1 % in diabetic patients as compared to controls, respectively (p < 0.02). After 12 weeks of fosinopril treatment, no differences in IVRT or A/E wave ratio were detectable between groups. ANP was enhanced in Type 1 diabetes as compared to controls (baseline: 9.2 +/- 3.0 vs. 4.5 +/- 1.1; exercise: 22.4 +/- 7.7 vs. 7.9 +/- 1.2; recovery: 20.3. +/- 4.6 vs. 9.5 +/- 2.0 fmol/ml, p < 0.02). Fosinopril treatment abolished any differences between groups. BNP plasma levels did not differ between groups and no exercise dependent changes were observed. NE- and E-increase was greater at 80 % .VO2 max work load in Type 1 diabetes than in controls (p < 0.05). Again, fosinopril abolished differences between groups. CONCLUSION: In Type 1 diabetes, impaired diastolic function is associated with elevated ANP and catecholamine plasma levels that are normalized after ACE inhibition. Thus, ANP but not BNP appears to be a sensitive biochemical marker for early diastolic dysfunction in Type 1 diabetes.     

肾大部切除、高盐摄食对SD大鼠脑心房钠尿肽的影响

为探讨脑内心房钠尿肽（ＡＮＰ）的作用,本工作采用ＳＤ大鼠,用放射免疫方法测定３／４肾大部切除与高盐摄食后脑内ＡＮＰ的含量。结果表明,对照组大鼠脑内ＡＮＰ分布广泛。３／４肾切除大鼠每日饮水量,尿量均比对照组高（Ｐ＜０．０５）,尿钠浓度低于对照组时,脑内ＡＮＰ含量尽管略有增加,但１０个核团（下丘脑室周核、弓状核、室旁核、视前室周核、中缝背核、尾壳核、杏仁核、脑桥背侧部、蓝斑和大脑皮质）ＡＮＰ含量和对照组无明显差别（Ｐ＞０．０５）。高盐摄食组每日饮水量和尿量均比对照组高,且尿钠浓度高于对照组,同时下丘脑室周核和弓状核ＡＮＰ含量比对照组高（Ｐ＜０．０５）。上述结果提示,大脑第三脑室前腹侧区（ＡＶ３Ｖ区）的ＡＮＰ可能在水盐调节上发挥重要作用。     

Identification of a 29-amino acid natriuretic peptide in chicken heart

Morphological and pharmacological observations have suggested that chicken atrial natriuretic peptide (ANP) is different from mammalian ANP. The present survey for the as yet unidentified ANP in chicken heart was performed by monitoring the relaxant effect on chick rectum. From the low molecular weight component of rectum relaxant activity observed in acid extracts of chicken ventricle, a novel 29-amino acid peptide was purified. The identical peptide was also isolated from acid extracts of chicken atrium. The peptide elicited a pharmacological spectrum very similar to that of mammalian ANP, including diuretic-natriuretic and hypotensive activity. Thus, the peptide was designated "chicken alpha-ANP (alpha-chANP)". The complete amino acid sequence determined for the peptide showed remarkable homology with that of mammalian alpha-ANP. However, maximum homology was observed when the peptide was compared with a recently identified porcine brain natriuretic peptide (BNP).     

The possible role of endogenous digitalis-like substance in the regulation of circadian changes in urinary electrolyte excretion in man

The urinary volume (U.V.), Na excretion (UNaV) and K excretion (UKV) have been reported to show a circadian rhythm in man, but the mechanism of this rhythm has not been made clear. To investigate how atrial natriuretic peptide (ANP) and endogenous digitalis-like substance (DLS) participate in the circadian change in urinary electrolyte, the circadian changes in ANP and DLS (digoxin-like immunoactivity: DLI, Na-K-ATPase inhibitor: ATPI, ouabain binding inhibitor to Na-K-ATPase: OBI) were evaluated in 5 normal man. ANP, DLI and OBI showed no significant correlation with urinary electrolyte excretion, but there was a significant positive correlation between plasma ATPI and urinary Na excretion. From these results it is suggested that circulating Na-K-ATPase inhibitor (plasma ATPI) may be involved in the regulation of the circadian rhythm of urinary Na excretion.     

Effect of vasoactive substances on natriuresis induced by atrial natriuretic peptide in isolated perfused rat kidneys

We studied the interaction between synthetic atrial natriuretic peptide (ANP) and various vasoactive substances, which included isoproterenol (ISO), aminophylline (AMI), and dibutyryl cyclic AMP (dBcAMP) as vasodilators, and angiotensin II (AII) and norepinephrine (NE) as vasoconstrictors, and prazosin as an alpha-blocker in isolated perfused rat kidneys (IPK). When 10(-9) mol of ANP was administered in 75 ml of a perfusate, the renal vascular resistance (RVR) was transiently decreased for 5 min, and increased thereafter. Simultaneously, ANP increased the glomerular filtration rate (GFR), urine flow (UV), absolute Na excretion (UNaV) and absolute K excretion (UKV). All of the above mentioned effects of ANP were significantly inhibited by administering ISO, AMI or dBcAMP. On the other hand, the administration of AII and NE significantly enhanced the increases in UV and UNaV and the fractional excretion of Na induced by ANP, although AII and NE had no influence on the changes in RVR and GFR induced by ANP. Prazosin did not modify the renal effects of ANP. These results suggest that the natriuretic effect of ANP is inhibited by agents that increase cyclic AMP in vascular smooth muscle cells. It is also suggested that the natriuretic effects of ANP can be explained by an increase in GFR and changes in intrarenal hemodynamics, rather than by the direct effect of ANP on renal tubules.     

In vitro enhancement of natural cytotoxicity by atrial natriuretic peptide fragment 4-28.

The presence of atrial natriuretic peptide (ANP) binding sites in the thymic cortex, medulla, and splenic white pulp suggests that this peptide may have immunoregulatory activity. We examined the effect of ANP on human natural killer (NK) cell activity. ANP significantly augmented NK cell cytotoxicity after twenty-four hours of incubation but had no effect on NK activity after short-term incubations of one hour. In addition, atrial natriuretic peptide did not effect the expression of natural killer or T cell surface markers. This study demonstrates that atrial natriuretic fragment 4-28 enhances natural killer cell activity.