植物提取剂福司柯林对心房钠尿肽分泌的调节作用

目的：观察从植物中提取的腺苷酸环化酶直接激活剂——福司柯林对心房钠尿肽分泌的影响及其机制。 方法：实验于2004—09／2005—09在吉林省延边大学医学部基础医学院生理学与病理生理学教研部完成。取大耳白兔26只，麻醉后立即开胸取出心脏，剥离左心房后固定心房灌流装置上，并给予适宜的电刺激使其搏动。利用体外灌流搏动的家兔心房做以下实验：①待心房搏动稳定之后，经过一个对照组循环（每12min定为一个实验循环），处理福司柯林（1μmol／L）3个循环。②经过一个循环对照组之后，先处理L-型Ca^2＋通道阻断剂硝苯地平（1μmol／L）或蛋白激酶非选择性抑制剂stau—rosporine（1μmol／L）3个循环，在硝苯地平或staurosporine存在下再处理福司柯林追加3个循环。以上实验均采用放射免疫技术和实时测定环-磷酸腺苷方法观察福司柯林对心房搏出量,环一磷酸腺苷逸出量及心房钠尿肽分泌的影响。 结果：①福司柯林（1μmol／L）明显抑制心房钠尿肽分泌（P＜0．01），同时显著增加心房搏出量和环一磷酸腺苷逸出量（P＜0．01）；在一定范围内，环-磷酸腺苷生成越多心房钠尿肽分泌越受抑制，并呈现线性关系（y=-5．268 X＋9．506，r^2=0．971，P＜0．001）。②硝苯地平（1μmol／L）未能改变福司柯林对心房钠尿肽分泌的抑制和促进环-磷酸腺苷的生成效应（P＜0．01），但显著抑制心房搏出量（P＜0．01），③staurosporine＋福司柯林明显增加环一磷酸腺苷逸出量（P＜0．01）的同时显著抑制心房钠尿肽的分泌（P＜0．01），但心房搏出量并没有受到环-磷酸腺苷生成增多的影响，且心房钠尿肽的分泌与staurosporine（第3个循环）相比并没有显著性差异。 结论：腺苷酸环化酶直接激活剂福司柯林主要通过蛋白激酶-依赖的信导拷导涂释抑制心房钠尿肽分泌。     

高K+缓冲液对家兔心房钠尿肽分泌的影响

目的 探讨细胞外高K+对家兔心房钠尿肽(ANP)分泌的影响及其作用机制.方法 取大耳白家兔18只,利用乌拉坦麻醉后立即开胸取出心脏,剥离左心房固定在心房灌流装置上,并给予适宜的电刺激使其搏动.待心房搏动稳定后(约60 min),分3组按照如下3种实验步骤进行实验:①6只家免经过1个对照循环(每12分钟定为1个实验循环),然后处理高K+缓冲液(K+浓度为5.64 mmol/L;缓冲液的渗透压保持不变)3个循环,之后恢复正常缓冲液2个循环;②6只家兔经过1个对照循环,处理L-型Ca2+通道阻断剂硝苯地平(1.0 μmol/L)3个循环;③6只家兔经过1个对照循环,先处理L-型Ca2+通道阻断剂硝苯地平(1.0 μmol/L)3个循环,然后在硝苯地平存在下同时处理高K+缓冲液3个循环.观察心房ANP分泌和心房搏出量的变化.ANP浓度采用放射免疫法进行测定.结果 ①高K+缓冲液明显增加心房ANP的分泌(P均<0.01),而心房搏出量则呈现下降趋势,但与对照循环相比差异无统计学意义(P0.05),当恢复正常缓冲液时ANP分泌量和心房搏出量趋于回复正常水平,与对照循环相比差异无统计学意义(P0.05);②L-型Ca2+通道阻断剂硝苯地平(1.0 μmol/L)显著增加心房ANP分泌(P<0.01或P<0.05)的同时明显降低心房搏出量(P<0.01或P<0.05);③L-型Ca2+通道阻断剂硝苯地平(1.0 μmol/L)完全阻断高K+缓冲液促进ANP分泌的作用(P<0.01或P<0.05),并进一步抑制心房搏出量(P均<0.01).结论 细胞外高K+缓冲液促进家兔搏动的离体心房ANP的分泌,其作用与细胞外高K+竞争性抑制细胞外Ca2+内流有关.     

砷剂防治哮喘气道炎症的分子机制：砷剂对丝裂原活化蛋白激酶磷酸酶基因表达作用的研究

目的：研究三氧化二砷对T细胞丝裂原活化蛋白激酶磷酸酶(mitogen-activated protein kinase phosphatase，MKP-1)基因表达的影响，探讨砷剂治疗哮喘气道炎症的分子机制。方法：本研究采用定量PCR的技术研究Hut-78 T细胞在不同浓度三氧化二砷(5μmol／L和1μmol／L)作用下，在不同时间段(3min，10min，20min，30min及1h)，T细胞内MKP-1 mRNA的表达水平。结果：Hut-78细胞在经过砷剂处理后，细胞内MKP-1 mRNA水平在10min即呈现上升的趋势。5μmol／L砷剂20min组和1 μmol／L砷剂20min组细胞内MKP-1 mRNA水平均明显高于对照组(t=5．947，P=0．001；t=2．561，P=0．035)，而在30min时。所诱导MKP-1 mRNA水平均达到高峰，其后均呈下降的趋势。而在时间段20min和1h，5μmol／L砷剂组要高于1 μmol／L组(t=3．056，P=0．0223：t=3．501，P=0．0128)。结论：三氧化二砷对MKP-1的基因表达具有上调作用；MKP-1为三氧化二砷作用的早期反应基因之一；砷剂对MKP-1的作用呈时间和剂量相关：小剂量的砷剂可能在哮喘的治疗和预防上具有重要的应用价值。     

心房钠尿肽对家兔急性呼吸窘迫综合征的作用及机制

目的:研究心房钠尿肽(ANP)对急性呼吸窘迫综合征中肺泡Ⅱ型上皮细胞(AT-Ⅱ)的保护作用.方法:24只家兔随机等分为对照组、内毒素(ET)组、ANP组.通过耳缘静脉给药,给药3 h后处死动物,收集肺泡灌洗液(BALF),测定BALF表面张力和总磷脂(TPL)、丙二醛(MDA)、总蛋白(TP)含量及乳酸脱氢酶(LDH)、碱性磷酸酶(AKP)活性.结果:与对照组比较,ET可使BALF中LDH活性[(618±174)U/L vs(1 104±294)U/L]及TP含量[(38±17)g/L vs(110±32)g/L]升高(P＜0.05),ANP可逆转此现象;ANP能逆转ET引起的MDA含量升高;ET可使BALF中TPL含量[(0.53±0.07)μg/kg vs(0.31±0.10)μg/kg]明显降低(P＜0.05)、表面张力[(20.8±3.0)mN/m vs(26.3±3.9)mN/m]升高(P＜0.05),ANP治疗后TPL[(0.45±0.08)μg/kg]升高、表面张力[(20.2±3.2)mN/m]降低;与对照组比较,ET组AKP活性[(0.10±0.08)U/L vs(0.36±0.10)U/L]升高(P＜0.05),ANP治疗后AKP[(0.14±0.09)U/L]明显降低.结论:ANP能减轻ET引起的急性呼吸窘迫综合征,其机制可能与ANP保护AT-Ⅱ并促进其分泌表面活性物质有关.     

砷剂防治哮喘气道炎症的分子机制:砷剂对丝裂原活化蛋白激酶磷酸酶基因表达作用的研究

目的:研究三氧化二砷对T细胞丝裂原活化蛋白激酶磷酸酶(mitogen-activatedproteinkinasephosphatase,MKP-1)基因表达的影响,探讨砷剂治疗哮喘气道炎症的分子机制。方法:本研究采用定量PCR的技术研究Hut-78T细胞在不同浓度三氧化二砷(5μmol/L和1μmol/L)作用下,在不同时间段(3min,10min,20min,30min及1h),T细胞内MKP-1mRNA的表达水平。结果:Hut-78细胞在经过砷剂处理后,细胞内MKP-1mRNA水平在10min即呈现上升的趋势,5μmol/L砷剂20min组和1μmol/L砷剂20min组细胞内MKP-1mRNA水平均明显高于对照组(t=5.947,P=0.001;t=2.561,P=0.035),而在30min时,所诱导MKP-1mRNA水平均达到高峰,其后均呈下降的趋势。而在时间段20min和1h,5μmol/L砷剂组要高于1μmol/L组(t=3.056,P=0.0223;t=3.501,P=0.0128)。结论:三氧化二砷对MKP-1的基因表达具有上调作用;MKP-1为三氧化二砷作用的早期反应基因之一;砷剂对MKP-1的作用呈时间和剂量相关;小剂量的砷剂可能在哮喘的治疗和预防上具有重要的应用价值。     

β淀粉样蛋白对神经干细胞酪氨酸蛋白激酶A表达的影响

目的:观察不同浓度的Aβ1-40对C17.2神经干细胞TrkA表达的影响方法:分别应用舍终浓度为0、20、40、60、80、100 nmol/L Aβ1-40的培养液孵育C17.2神经干细胞24 h,MTT法检测各组细胞活性,Western blot观察各组神经干细胞TrkA表达情况.结果:MTT法检测结果显示各组细胞活性差异不明显;Western blot结果显示终浓度为20、40、60 nmol/L Aβ1-40组的神经干细胞TrkA表达有不同程度的增加,100 nmol/L Aβ1-40组细胞TrkA表达较对照组减少,80 nmol/L Aβ1-40组细胞TrkA表达较对照组差异无统计学意义.结论:Aβ1-40对神经干细胞TrkA表达的影响呈浓度依赖性.     

降钙素对大鼠颅骨成骨细胞调控作用的体外观察

背景:降钙素是强有力的破骨细胞抑制剂,可直接、快速而广泛地抑制骨吸收,近年来有学者报道其有促进骨折愈合的功能,推测降钙素对成骨细胞也有直接的作用.目的:体外观察降钙素对大鼠成骨细胞的药理作用,分析其是否通过细胞外信号调节激酶信号通路产生.设计、时间及地点:分组对照观察,于2007-06/2008-05在南京医科大学药理学实验室完成.材料:选用新牛SD大鼠,分离培养颅骨成骨细胞.方法:取第2代成骨细胞进行分组实验:0.01μg/L降钙素组、0.1 μg/L降钙素组、1 μg/L降钙素组分别加入不同剂量降钙素进行干预,U0126+1 μ9g/L降钙素组提前30 min加入100 μmol/L的细胞外信号调节激酶抑制剂U0126,并设空白对照组.主要观察指标:通过四甲基偶氮唑盐比色法、对硝基苯磷酸盐法和钙结节茜素红染色法分别检测降钙素对成骨细胞的增殖、分化、矿化能力的影响;应用反转录-聚合酶链反应技术检测促骨形成关键基因核心结合因子a1 mRNA的表达情况;应用Western Blotting技术检测磷酸化细胞外信号调节激酶1/2蛋白表达情况.结果:加入0.01,0.1,1 μg/L的降钙素干预后,成骨细胞的增殖、分化、矿化能力以及核心结合因子a1 mRNA的表达均随降钙素剂量增加而增强,且0.1,1 μg/L组与空白对照组比较差异具有显著意义(P<0.05～0.01);此外降钙素促进了磷酸化细胞外信号调节激酶1/2蛋白的表达(P<0.05).U0126可阻断以E所有效应(P<0.05～0.01).结论:降钙素可能通过细胞外信号调节激酶信号通路调控促骨形成关键基因核心结合因子al mRNA的表达,进而促进成骨细胞的增殖、分化、矿化能力.     

不同强度的游泳训练对脑缺血再灌注大鼠蛋白激酶A表达的影响

目的 探讨强化游泳训练对脑缺血再灌注大鼠神经功能及蛋白激酶A(PKA)表达的影响.方法 采用线栓法建立左侧大脑中动脉阻塞(MCAO)2 h再灌注动物模型.120只造模成功的雄性SD大鼠按随机数字表法分为训练1组、训练2组、训练3组和MCAO对照组,每组30只.训练1组大鼠每日游泳5 min,训练2组大鼠每日游泳10 min,训练3组大鼠每日游泳20 min;MCAO对照组大鼠不给予任何训练.另选30只大鼠为假手术组,不阻塞大脑中动脉血流,不给予任何训练.以上5组大鼠又分别随机分为术后3、7和14 d三个时间点亚组,每个时间点10只大鼠.分别于术后3、7和14d三个时间点,采用Menzies神经行为评分和前肢放置试验评价各亚组大鼠神经功能缺损情况,采用免疫组织化学方法测定各亚组大鼠脑缺血再灌注后脑内PKA阳性细胞的表达率,采用RT-PCR的方法测定各亚组大鼠脑缺血侧大脑皮质PKA的mRNA表达量,并进行统计学分析比较.结果 假手术组神经功能正常.MCAO对照组各时间点的神经功能评分与假手术组同时间点比较,组间差异均有统计学意义(P＜0.05);各训练组分别在训练3、7和14 d后的神经功能改善情况优于同时间点MCAO对照组;训练3组训练14 d后受损神经功能改善最明显(P＜0.05),其训练3、7和14 d后的Menzies评分分别为(1.40±0.55)、(1.00±0.71)和(0.80±0.45)分,前肢放置试验评分分别为(5.20±0.84)、(3.80±1.30)和(2.40±1.14)分.训练1、2和3组各时间点的PKA阳性细胞表达率及其mRNA表达量高于同时间点MCAO对照组;且训练3组训练14d后的PKA阳性细胞表达率及其mRNA表达量增加较其它各训练组更为明显(P＜0.05),其训练3、7和14 d后的PKA阳性细胞表达率分别为(32.84±1.66)％、(35.05±1.33)％和(45.92 ±2.03)％,PKA mRNA表达量分别为(32.18±0.86)％、(37.44±1.27)％和(42.77±0.81)％.结论 强化游泳训练可以增加脑缺血再灌注大鼠PKA阳性细胞表达率及其mRNA表达量,改善受损神经功能,促进感觉和运动功能恢复.     

高血糖状态对大鼠骨骼肌和心肌C-Jun氨基末端激酶和p38信号转导系统的影响

目的:探讨高血糖状态对大鼠骨骼肌和心肌C-Jun氨苯末端激酶(C-JunN-terminalkinase,JNK)和p38激酶活性的作用,进一步了解糖尿病的发病机制,为糖尿病的临床康复治疗提供一些理论依据。方法:12周龄、体质量200～230g的SD大鼠12只,根据是否注射链脲佐菌素(streptozotocin,STZ)随机分为高血糖组(n=6)和正常血糖组(n=6)。高血糖组大鼠腹腔内注射STZ(65mg/kg)建立持续高血糖模型(血糖>16mmol/L)。正常血糖组大鼠不注射STZ,维持正常血糖。运用化学发光法测定骨骼肌和心肌JNK和p38活性。结果:骨骼肌和心肌JNK活性在高血糖组明显增高,分别高于正常血糖组1.8倍和1.4倍。骨骼肌和心肌p38活性在高血糖组分别高于正常血糖组的2.0倍和1.6倍。结论:高血糖状态可以激活骨骼肌和心肌JNK和p38信号转导通道。提示细胞信号转导系统参与了糖尿病的发病机制。     

胰岛素增敏剂对糖尿病患者胰岛素受体激酶的影响

目的针对糖尿病患者胰岛素受体缺陷导致的胰岛素抵抗,观察胰岛素增敏剂罗格列酮和吡格列酮对2型糖尿病患者胰岛素受体蛋白酪氨酸激酶活性的影响。方法实验于2001-10/2003-03在东南大学基础医学院生化教研室完成。应用W GA-Sepharose4B亲和层析方法分离纯化来自正常人16例、糖尿病患者16例、肥胖症患者22例3组人群的血红细胞膜胰岛素受体,分别在罗格列酮或吡格列酮作用下应用同位素示踪法测定受体蛋白酪氨酸激酶活性的变化,激酶活性用多肽底物磷酸化的程度表示。结果16例正常人,16例糖尿病患者,22例肥胖症患者的血样均进入结果分析。①正常人、糖尿病患者、肥胖症患者3组红细胞膜受体蛋白酪氨酸激酶活性均呈胰岛素剂量依赖关系。②与正常对照组相比[(781.86±120.23)fm ol/(m g·m in)],糖尿病组与肥胖症组的红细胞膜蛋白酪氨酸激酶和纯化胰岛素受体蛋白酪氨酸激酶的活性均显著降低[(230.09±35.87),(253.57±37.38)fm ol/(m g·m in)]。吡格列酮和罗格列酮均可以明显改善糖尿病患者和肥胖症患者的纯化胰岛素受体蛋白酪氨酸激酶的活性[(830.63±166.96),(800.79±153.45)fm ol/(m g·m in),P<0.01;(664.92±119.33),(567.98±103.47)fm ol/(m g·m in),P<0.01]。结论罗格列酮和吡格列酮可能部分通过直接激活胰岛素受体蛋白酪氨酸激酶的活性来改善胰岛素敏感性。     

Pulsatile secretion of atrial natriuretic peptide and brain natriuretic peptide in healthy humans.

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are involved in sodium and water homoeostasis in healthy humans. The plasma concentrations of the natriuretic peptides can be used to differentiate between dyspnoea of cardiac and pulmonary origin, and the degree of elevation of the peptide levels in the plasma in heart failure is a measure of the severity of the disease. However, the patterns of secretion of ANP and BNP are not clear either in healthy humans or in patients. The purpose of the present study was to test the hypotheses that both ANP and BNP are secreted in pulses in healthy humans, and that this phenomenon can be revealed by determination of ANP and BNP in peripheral venous blood samples. In 12 healthy subjects, blood samples were drawn every 2 min through an intravenously inserted plastic needle over a period of 2 h. Plasma concentrations of ANP and BNP were determined by RIAs, and the results were analysed for pulsatile behaviour by Fourier transformation. Pulsatile secretion of ANP was seen in 10 out of 12 subjects [nu=0.028 min(-1) (median; range 0.013-0.047 min(-1)), i.e. a pulse of ANP with an interval of 36 min (range 21-77 min)]. Pulsatile secretion of BNP was seen in nine out of 12 patients [nu=0. 021 min(-1) (range 0.013-0.042 min(-1)), i.e. a pulse of BNP with an interval of 48 min (range 24-77 min)]. The main conclusion is that the secretion patterns of both ANP and BNP are pulsatile in most healthy humans. Consequently, it is important to study whether pulsatile secretion also occurs in heart failure in order to obtain the most informative predictive values both in the differential diagnosis of dyspnoea and in the evaluation of the severity of the disease.     

Variable patterns of atrial natriuretic peptide secretion in man

Abstract Peripheral circulating levels of atrial natriuretic peptide may exhibit short-term variation compatible with a pulsatile pattern of secretion. We obtained samples every 2 min for 90 min from the antecubital vein of 16 patients with chronic cardiac failure and 13 controls. Overall levels were higher in the patients (median and quartiles 230 (125,325) vs. 26 (16,48) ng l^-1; P <0·001). In both groups there was considerable variability, with 10 (2–12) peaks, 9 (7–15) troughs (both defined as >2 SD from the mean) and 16 (13–18) pulses (defined by computer) during the sampling period in controls, and a similar number in patients. We then carried out simultaneous sampling in the pulmonary artery, femoral artery and peripheral vein in eight subjects with normal cardiac function and six patients with impaired function due to valvular heart disease. The pattern of variability was preserved in all three sites in both groups, suggesting intermittent secretion rather than variable breakdown of the peptide in the lung. No changes in right atrial pressure or heart rate were observed to coincide with the variations, but levels of the peptide in the pulmonary artery correlated with right atrial pressure in patients (r = 0·87; P <0·05). The mechanism of such periodicity and its pathophysiological importance remain unknown.     

Lack of effect of atrial natriuretic peptide on vasopressin release

This study was designed to investigate the effects of intracerebroventricular or intravenous atrial natriuretic peptide (ANP) on plasma arginine-vasopressin (AVP) levels, plasma renin activity (PRA), blood pressure (BP) and heart rate (HR) in conscious rats. No changes were observed in plasma AVP levels and PRA after intracerebroventricular injection of ANP (0.3 nmol/kg). Also no changes were found in BP and HR after intracerebroventricular ANP injection in the dose range 0.01-0.3 nmol/kg. No significant changes were observed in plasma AVP levels after the intravenous administration of ANP at 2.5 nmol/kg to hydrated rats or at 0.1 nmol/kg and 2.5 nmol/kg to dehydrated rats, although the larger dose was sufficient to cause a small fall in BP. Even after 30 min intravenous infusion of ANP at 0.1 nmol min-1 kg-1, a dose sufficient to produce very high plasma ANP levels, no change in plasma AVP could be detected, although haemodynamic changes were observed. Intravenous ANP injection (2.5 nmol/kg) inhibited basal renin secretion in hydrated rats and also inhibited renin secretion which had been stimulated by prior dehydration. From these studies in hydrated and dehydrated rats, there was no evidence that either intracerebroventricular or intravenous ANP administration affected AVP release in vivo.     

Gene expression and secretion of atrial natriuretic peptide by murine macrophages.

An increased expression of atrial natriuretic peptide (ANP) has been reported in activated macrophages of the acutely involuted rat thymus. We communicate here that ANP may reflect a common constituent of macrophages, as mRNA coding for ANP is present in peritoneal- as well as in bone marrow-derived macrophages (PM, BMM). Furthermore, both types of macrophages synthesize and release ANP which was found to mainly represent the biologically active fragment ANP99-126. ANP expression in macrophages is regulated by compounds affecting the activity of these immune cells. For example, incubation of PM or BMM in vitro with LPS and zymosan, respectively, increased ANP-mRNA up to sixfold as determined by competitive PCR quantification. Exposure of macrophages to dexamethasone (Dex, 10(-7) M) elicits moderate effects (1.4-fold), while PMA (10(-7) M) failed to affect its abundance. These findings are complemented by data regarding ANP synthesis and secretion. Incubation of macrophages with LPS, Dex or a combination of both results in an up to 3.5-fold increase of intracellular ANP99-126 (basal 10 fmol/mg protein), and an up to 6.6-fold increase of its secretion (basal 40 fmol/mg protein, 24 h). Since macrophages synthesize and release ANP, the peptide may be involved in the complex mechanisms of host defense, a major function of these immune cells.     

Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide.

We have examined the effects of several PGs on the synthesis and release of the atrial natriuretic peptide (ANP) in vivo and in vitro. PGF2 alpha infusion in anesthetized rats resulted in a significant increase in plasma immunoreactive (ir) ANP levels in vivo despite effecting only modest changes in hemodynamics. The PGs were also effective at promoting irANP secretion in primary cultures of neonatal rat atrial and ventricular cardiocytes. PGF2 alpha increased irANP release with half-maximal induction seen at approximately 10(-8) M; PGE2 was somewhat less effective and prostacyclin (PGI2) was without effect. The PGs also increased ANP mRNA levels in these cells, suggesting that these agents exert a major effect on the synthesis as well as the secretion of the prohormone. Transient expression analysis of atrial cells transfected with 2,500 bp of human (h) ANP 5' flanking sequence linked to a chloramphenicol acetyltransferase (CAT) reporter demonstrated that PGF2 alpha (10(-5) M) increased hANP promoter activity approximately twofold relative to the control. PGF2 alpha had no effect on the promoterless control (pSV0-lamin CAT). Treatment of cultured atriocytes with high concentrations of a cyclooxygenase inhibitor resulted in a significant suppression of ANP secretion in vitro and a truncation of the plasma ANP response to volume infusion in vivo. Taken together these studies support a role for PGs as regulators of cardiac ANP synthesis and secretion, and suggest an additional mechanism whereby eicosanoids may act to control cardiovascular and renal homeostasis.     

Cardiac secretion and renal clearance of atrial natriuretic peptide in normal man: effect of salt restriction

1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+/- 14, P less than 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED +/- 0.33, P less than 0.05). Brachial mean arterial pressure fell by 6% (P less than 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P less than 0.01), whereas arterial ANP concentrations fell by 39% (P less than 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (SED +/- 74, P less than 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P less than 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion.