Effects of exogenous renin and sodium load on renin activity in unilaterally nephrectomized rats

Summary Effects of injection of homologous renin and sodium load given through 1.5% saline as drinking water on plasma renin activity and renin content of the kidneys were studied in rats with intact kidneys (group A) and in unilaterally nephrectomized rats (group B). During an experimental period of 10 days, blood pressure was measured four times. At the end of the experiment, the plasma renin activity and the renal content of renin were determined.Renin injection did not cause a rise in blood pressure in both groups. In unilaterally nephrectomized rats, renin content of the remaining kidney increased significantly. This increase was suppressed either by the renin injection or the salt load, whereas neither the renin injection not the salt load affected renal content of renin in group A. In unilaterally nephrectomized rats, the renin injection or the sodium load induced a significant decrease in plasma renin activity when compared to rats in group A.     

Role of the retention of water and sodium in two types of experimental renovascular hypertension in the rat

Summary The effect of either removing the clamped kidney or unclamping the renal artery on hypertension induced by partial constriction of one renal artery with (one-kidney Goldblatt hypertension) or without contralateral nephrectomy (two-kidney Goldblatt hypertension) was studied in rats, and the influence of unclamping on urinary water and electrolyte excretion was measured. In one-kidney Goldblatt hypertension, removal of the clamped kidney lowered blood pressure in the initial stage (first week), but had no significant effect on established hypertension. In contrast, unclamping rapidly and permanently normalized blood pressure in the chronic stage, and induced a transient, marked increase of urinary excretion of water, sodium and potassium. Ligating the ureter immediately before unclamping prevented the permanent (24 h) fall in arterial pressure, but did not abolish an initial (6 h) fall of blood pressure. In two-kidney Goldblatt hypertension, removal of the clamped kidney consistently caused a rapid return of the arterial pressure to normal, irrespective of the duration of hypertension, and unrelated to the excetory function of the contralateral kidney. Hypertensive rats of this type excreted significantly more sodium, potassium and water than control rats. Unclamping normalized blood pressure and did not significantly increase urinary sodium and water excretion, but sharply decreased potassium excretion.Supported by Fonds National Suisse de la Recherche Scientifique, Grants No. 5313.3 and 3369.70.Preliminary communications: Liard, 1969 [25]; Liard and Peters, 1970 [27].     

Role of the peritubular oncotic pressure on sodium excretion by the avian kidney

Summary The introduction of oncotically active substances, such as dextran and human serum albumin, into the renal portal vein of the cock is followed by a reduction of sodium excretion rate by the injected kidney, the contralateral organ acting as control. This observation demonstrates that the transtubular oncotic pressure gradient plays some role in sodium transport by the renal tubules. The implications of this finding are confronted with the clearance and micropuncture data obtained in the course of saline diuresis in other species.     

Influence of serumalbumin and dextran on sodium and water excretion by the isolated dog kidney

Summary The addition of serumalbumin or of dextran reduces sodium and water excretion by isolated kidneys submitted to a saline load. While dextran supplementation produces a considerable drop of glomerular filtration, serumalbumin supplementation induces only slight changes in filtration; a proportional increase of tubular reabsorption is observed. The difference between the response to dextran and serumalbumin may be related to differences in intrarenal blood circulation. Changes in plasma protein concentration play a role in autonomous renal response to saline loading and influence tubular sodium reabsorption. This autonomous renal response is primarily related to plasma dilution.This work has been performed with the help of the Fonds National de la Recherche Scientifique.     

Effect of the angiotensinogen genotype on experimental hypertension in mice

Polymorphisms of the angiotensinogen (Agt) gene may affect blood pressure. We used a mouse model to test for the role of the Agt genotype in low-renin or high-renin forms of hypertension. Mice bearing one, two, three, or four copies of the Agt gene underwent renal artery clipping to induce high-renin two-kidney, one-clip renovascular hypertension (2K1C), or uninephrectomy, salt loading, and application of deoxycorticosterone-acetate (DOCA) pellets to induce low-renin mineralocorticoid hypertension. Appropriate control animals were also studied. Blood pressure was measured by tail cuff as well as by direct intra-arterial recordings. There was a small effect of the Agt genotype on baseline blood pressure before induction of hypertension. The extent of 2K1C hypertension was not affected by the genotype. In contrast, there was a marked gene-dose effect on DOCA-hypertension (21.2 mmHg over all genotypes). Treatment of DOCA mice with the angiotensin II type 1 receptor antagonist abolished the genotype effect on blood pressure and left ventricular hypertrophy. There was a trend towards less suppression of endogenous aldosterone by DOCA treatment with increasing number of Agt gene copies. We conclude that the Agt genotype exerts a marked effect on blood pressure in a low-renin form of hypertension but no effect in the face of stimulated renin, at least in mice.     

Single glomerular filtration rate of superficial and Juxta-medullary nephrons in the rat during different types of arterial hypertension

Summary The single nephron glomerular filtration rate (SNGFR) of superficial (S) and juxtamedullary (JM) nephrons were measured using¹⁴C-ferrocyanide infusion technique in rats under 3 different states of hypertension: acute hypertensions obtained either by bilateral carotid clamping (CC) or by contralateral renal ischemia (CI), and chronic Goldblatt hypertension. The juxtaglomerular index (JGI) was determined on the experimental kidneys.During acute hypertensions the JGI was normal, the granularity being more marked for the superficial than for the deep cortex. SNGFRs were higher in the JM (CC=39.2±3.4 SE nl/min; CI=41.0±4.5) than in the S (CC=30.3±2.5 CI=30.3±3.0) nephrons. These values are not different from those of normal rats. In the untouched kidney of Goldblatt rats the JGI was equal to zero. There was a general increase in SNGFRs. This increase was more marked for the S than for the JM nephrons, and the SNGFRs equalized in these two categories of nephrons (S=73.0±8.4; JM=74,7±8.2).From these observations, it is suggested that the renin content of the juxtaglomerular apparatus may play some role in the absolute value and intrarenal distribution of SNGFRs.This work was supported in part by a grant D.G.R.S.T. No. 7172 2726.Chargé de recherches à l'INSERM.     

缺血与再灌注对大鼠肾脂质过氧化物含量和钠,钾浓度的影响

本研究用成年雄性Wistar大鼠,作肾缺血和再灌注实验;发现:(1)缺血60分钟组的肾皮质脂质过氧化物含量(MDA76.05±18.14nmol/g)显著降低(P<0.001),钠浓度(97.43±10.20mEq/L)显著增高(P<0.01)而钾浓度(74.68±6.36mEq/L)显著降低(P<0.002)。(2)缺血60分钟再灌注30分钟组的肾皮质,脂质过氧化物含量(147.25±17.18nmol/g)显著增加(P<0.01),钠、钾浓度接近正常值(79.61±18.44和90.33±6.13mEq/L)。缺血与缺血再灌注肾皮质其脂质过氧化物含量同钠钾浓度之间无显著相关。实验提示:(一)缺血再灌注肾氧自由基“爆发性”生成所引发的脂质过氧化可能是肾缺血后损伤的重要机制之一。(二)缺血肾内钠、钾浓度变化似能反映缺血引起的细胞膜钠泵失灵及细胞内外离子分布异常。这种变化同氧自由基生成和脂质过氧化强度之间,似无直接因果关系。     

Effect of raising the transtubular oncotic gradient on sodium excretion in the dog

Summary In dogs treated with high doses of aldosterone and pitressin, sodium excretion is reduced following the rise in the transtubular oncotic pressure gradient induced either by systemic injections of albumin or dextran or by systemic infusion of small amounts of adrenalin. This effect is obtained under conditions of a constant filtered sodium load. The increased tubular sodium reabsorption is not accompanied by any change in renal oxygen consumption and is independent of plasma volume changes. These results demonstrate that a small fraction of filtered sodium is reabsorbed by a process governed by the transtubular oncotic pressure gradient.     

Blood pressure in essential hypertension correlates with the concentration of a circulating inhibitor of the sodium pump

Summary The influence of serum from patients with essential hypertension on the sodium efflux rate constants of human lymphocytes and on the activity of isolated (Na⁺+K⁺)-ATPase was investigated. The ouabain-sensitive sodium efflux rate constant was significantly decreased (p<0.001) in the sera of 19 hypertensives (1.92±0.11 h^–1) compared with the sera of 30 normotensives (2.44±0.07 h^–1). The ouabain-insensitive sodium efflux was unaffected. These results corresponded with a significant difference (p<0.005) of (Na⁺+K⁺)-ATPase activity (1.03±0.04 mU/ml and 0.079±0.06 mU/ml), when an isolated (Na⁺+K⁺)-ATPase was incubated with the sera of 22 normotensives or 18 hypertensives. Both the rate constant of ouabain-sensitive sodium efflux and the (Na⁺+K⁺)-ATPase activity correlated significantly with the diastolic and systolic blood pressure (p<0.001). These data, therefore, demonstrated the close relationship between essential hypertension and the concentration of a circulating inhibitor of the sodium pump.Abbreviations ATP Adenosine triphosphate - EGTA Ethyleneglycol bis(2-aminoethyl)-N,N,N,N-tetraacetic acid This paper contains an essential part of the thesis of K.M. presented to the Fachbereich Veterinärmedizin, GiessenThis work was supported by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg (Scho 139/16-2) and by the Fonds der Chemischen Industrie, Frankfurt/Main     

Effects of indomethacin on renal hemodynamics and on water and sodium excretion by the isolated dog kidney

Summary Blood-perfused isolated dog kidneys demonstrate steady increases in blood flow and in water and sodium excretion which could be attributed to the accumulation of renal prostaglandins in the perfusing blood. This hypothesis was tested by adding indomethacin, a potent inhibitor of prostaglandins synthesis, to the perfusing blood.Indomethacin completely prevented the vasodilation observed in control kidneys, without affecting glomerular filtration rate. Urine volume was not modified but sodium excretion was enhanced while the steady free water clearance increment observed in the control kidneys was depressed by indomethacin. The sum of sodium and free water clearances which, in the absence of antidiuretic hormone, constitutes an index of the part of the filtered load of solutes which escapes proximal tubular reabsorption, was not modified by indomethacin. Finally, indomethacin partially maintained the osmotic cortico-papillary gradient which was abolished after 2 hrs perfusion in control kidneys.These data suggest that prostaglandins accumulation in the blood is probably the major cause of the vasodilation taking place in isolated blood-perfused kidneys. This vasodilation does not account for decreased proximal reabsorption but partially explains the ADH-resistant diabetes insipidus developing in the isolated kidney. Moreover, indomethacin inhibits sodium reabsorption in the ascending limb of Henle's loop and increases water transport in the collecting duct.     

Effects of sodium on the calcium paradox in rat hearts

Reduction of the Na concentration in the Ca-free perfusion solution reduces the amount of myoglobin released by the cells when Ca is readmitted if sucrose is used to replace NaCl under mild hypothermia. When salts like cholinechloride or LiCl are used instead of sucrose, no protection is seen at any temperature. The temperature threshold above which myoglobin loss sharply increases is lowered by prolonged Ca depletion or by the addition of EGTA to the Ca-free solution. Protection by sucrose does not occur in the presence of EGTA. An increase of cell Na induced by strophanthidin during the Ca depletion phase has no effect on myoglobin release. The exponential decline in twitch tension in the early phase of Ca deprivation has the same half-live (T _1/2) for Ca-free solutions containing 145 mM Na or 35 mM Na (110 mM Li or choline), but itsT _1/2 is prolonged if sucrose is used to replace NaCl. When 5 mM EGTA is added to the Ca-free solutions, theT _1/2 is shortened and is not changed by the replacement of NaCl with sucrose. The rate of washout of Ca within the first 20 s of Ca depletion has a similar time course in a normal Na or in a Li and low Na solution. In a sucrose and low Na solution the rate of the Ca efflux is reduced. The addition of EGTA increases this rate and abolishes the slowing effect of a sucrose and low Na solution. Therefore myoglobin release during the Ca paradox does not depend on the Na gradient across the sarcolemma. Na⁺, like other cations, probably enhances the displacement of Ca²⁺ from critical binding sites during Ca-free perfusion, which predisposes the cells to the paradox.     

The role of the kidney in the development of hypertension a transplantation study in the prague hypertensive rat

It has been shown that genetic hypertension in rats usually travels with the kidney. To elucidate the mechanism of this phenomenon further, experiments were carried out in the Prague hypertensive (PH) rat, a model of genetic hypertension derived from the Wistar strain, in which a normotensive parallel, the Prague normotensive (PN) rat, was also bred from the same parent pair. Thus, it is possible to transfer organs between both parallels without substantial signs of rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy and transplantation of one kidney between PH and PN rats, did not affect the arterial blood pressure (BP). Transplantation of one kidney from PN rats to bilaterally nephrectomised PH rats normalised the high BP. If a PH rat was left with one original kidney in situ after the transplantation of a normotensive kidney, the high BP persisted until the original hypertensive kidney was removed. This removal resulted in sustained normalisation of BP. When the development of high BP in the PH rats was prevented for 2 months after weaning by antihypertensive drugs, transplantation of kidneys from these rats to bilaterally nephrectomised PN rats always induced a sustained hypertension in the recipient. These results argue against a role of high-BP-induced damage to the kidney and against an intrinsic increase in the salt-reabsorptive capacity of the tubular epithelium in PH rats. The data support the view that the kidney from PH rats produces a hypertensinogenic substance, the secretion of which is genetically determined and is not influenced by the magnitude of the BP.     

Urea and sodium: Effect on microsomal ATPase in different parts of the kidney

Summary Microsomal ATPase activity was studied in three regions of the rat kidney: cortex, medulla and papilla. (Na+K)-ATPase activity was highest in the medulla but a substantial activity, comparable to that in the cortex, was also present in the papilla. In the presence of high sodium (200–320 mM) or urea (100–900 mM) progressive inhibition of Mg-ATPase activity was observed in all three regions of the kidney.Urea (900 mM) or Na (320 mM) caused activation of (Na+K)-dependent ATPase in the medulla and inhibition of this enzymatic activity in the papilla of the kidney. Total microsomal ATPase activity in the medulla was unchanged in the presence of urea or sodium but was reduced in the papilla.Urea inhibited non-selectively Mg-p-nitrophenylphosphatase and K-activated p-nitrophenylphosphatase in all three parts of the kidney.These findings may point to a molecular basis for the function of urea and of sodium in the concentrating mechanism of the kidney.This study was supported by the Research Fund of the Israeli Ministry of Health.     

Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats

The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys. The abundance of renin mRNA in adrenal tissue was low and was estimated to be around 1% of that found in the kidneys. Adrenal renin mRNA levels also increased in animals kept on a low-salt diet and decreased in animals on high-salt diet. Taken together, our findings suggest that renin secretion and renin gene expression are inversely related to salt intake and that the influence of salt diet on these parameters has both transient and constant temporal components. Changes of blood pressure or nerve activity are not likely mediators of the effect of salt intake on renin expression. Since renal and adrenal renin mRNA levels change in parallel in response to alterations of salt intake we hypothesize the existence of a humoral factor that links renin expression to the rate of salt intake.     

Possible contribution of impaired sodium excretion to the development and maintenance of hypertension: a study of the isolated kidneys of the Prague hypertensive rat

 We have shown previously that in the Prague Hypertensive Rat (PHR) ”hypertension travels with the kidney” and that the kidney appears to produce an as yet unknown ”hypertensogenic” substance. Since enhanced sodium retention could also contribute to this type of hypertension, this possibility was tested in isolated perfused kidneys from PHR and from its normotensive substrain, PNR, bred from the same parent pair as PHR, at two levels of perfusion pressure (PP), i.e 110 and 150 mmHg (where 1 mmHg = 133.3 Pa). Young (6-week-old) and adult (12-week-old) animals of both substrains were used. In young PHR and PNR, there was no significant difference in haemodynamic parameters when the kidneys were perfused at either low or high PP. Surprisingly, water and sodium excretion rates were also the same at both PP values in both substrains, which thus – at this age – do not exhibit the well known ”pressure diuresis and natriuresis”. In adult PNR, perfusate flow and glomerular filtration rates (GFR) were independent of the level of PP (autoregulation) whereas water and sodium excretion rates were significantly higher at 150 than at 110 mmHg, a finding similar to those found in vivo studies (pressure diuresis and natriuresis). In adult PHR, however, both perfusate flow rate and GFR were pressure dependent: only at the high PP were values of both GFR and perfusate flow obtained which were similar to those in the PNR at low pressure. Sodium excretion was lower, and its tubular reabsorption higher, in PHR than in PNR at both levels of perfusion. Again, in PHR, the higher PP was needed to achieve the same rate of sodium excretion as in PNR at the lower pressure. Thus, the kidneys of PHR retain sodium at a given PP compared with the kidneys from PNR. This may contribute to the development and/or maintenance of hypertension in the PHR. Received: 21 February 1997 / Accepted: 28 May 1997     

Effect of sodium concentration and plasma sugar concentration on hexose absorption by the rat jejunum in vivo

The sodium-dependency of both the saturable and non-saturable components of glucose and galactose absorption across the rat jejunum in vivo has been determined. The non-saturable process appears to be unaffected by sodium removal but when Na⁺ concentrations in the lumenal fluid are progressively reduced from 143 mM to 0 mM theJ _max for active absorption is greatly decreased.In a separate study these two components of glucose transport were further investigated using intravenous sugar infusion to modify the transepithelial sugar concentration gradient. When identical glucose concentrations were present in plasma and intestinal lumen, the reduction in glucose absorption was fully accounted for by the elimination of the non-saturable component from the overall absorptive process. Together, these observations can be interpreted as further evidence for the existence of at least two absorption processes in vivo. The implication for analysing results from experimental studies of intestinal sugar absorption in vivo is discussed.     

小管间质肌成纤维细胞激活对大鼠残余肾硬化的影响

目的：本文研究５／６肾大部切除大鼠肾小管间质肌成纤维细胞（ｍｙｏｆｉｂｒｏｂｌａｓｔ，ＭＦＢ）标记性抗原，α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈ ｍｕｓｃｌｅ ａｃｔｉｎ，α－ＳＭＡ）免疫组化表达及其意义。方法：成年雄性Ｗｉｓｔａｒ大鼠（６－８周龄，２００－２５０ｇ）随机分成两组：１．假手术（ｓｈａｍ，ｎ＝５）ｍ，；２，ＳＸｎ 组（ｎ＝５）。     

一氧化碳对低氧性肺动脉高压的效应

目的:探讨外源性低浓度一氧化碳(CO)在低氧性肺动脉高压中的作用。方法:60只Wistar大鼠随机分为常氧组、低氧组、血晶素组、锡原卟啉组和低浓度CO组,每组12只。处理完毕后,右心导管法测定肺动脉平均收缩压和右心室压。杀鼠取肺组织,应用分光光度法测定肺组织HO-1活性,并进行常规免疫组织化学染色,应用逆转录多聚酶链式反应测定测定肺组织的HOmRNA水平。结果:①低浓度CO组肺动脉压为(18.52±3.24)mmHg,明显低于低氧组但仍高于常氧组(均为P＜0.01);②低浓度CO组HO-1活性为(1052.48±308.49)nmol·g^-1(protein),显著高于正常组(P＜0.01);③低浓度CO组HO-1蛋白表达水平均高于常氧组和低氧组(P＜0.01);④低浓度CO组HO-1mRNA水平的光密度值为2.63±0.18,显著高于正常组(P＜0.01)。结论:CO-HO系统参与了低氧性肺动脉高压的发病机制;低浓度CO可以有效促进HO-1mRNA表达,使HO-1活性和蛋白表达水平升高,进而部分降低肺动脉压力。     

The effect of a protein-free diet on the renin-angiotensin system in the rat

Summary The effects of a protein-free diet were studied in the rat. It was shown that the diet led to a decrease in total serum protein, in plasma renin activity, in plasma renin substrate and in blood pressure; and to an increase in haematocrit.A significant linear correlation was found in every combination between the total serum protein, plasma renin activity, plasma renin substrate and systolic blood pressure.In contrast to the plasma renin activity, the renin concentration in the kidney of rats on a protein-free diet was found not to be lower that of the control group.The protein-free diet caused a decrease in the pressor response to injected angiotensin II.     

Effects of calcium and sodium on contracture tension in the smooth muscle of the rat portal vein

Summary The purpose of the present study was to determine the quantitative relationship between membrane potential (or [K⁺]₀) and contracture tension in the smooth muscle of the rat portal vein, and to examine the influence of Ca⁺⁺ and Na⁺ on this relationship. However, electrical all-or-none responses were successfully abolished only in Na⁺-free sucrose-Krebs due to hyperpolarization and in K⁺-high Krebs due to depolarization. It did not seem possible to eliminate spike discharge at intermediate levels of membrane potential without the simultaneous loss of contractility. In the hyperpolarized state the muscle remained relaxed despite the very low levels of [Na⁺]₀ and despite increases in [Ca⁺⁺]₀ up to 20 mM. The depolarized portal vein developed a contracture which was intimately dependent on [Ca⁺⁺]₀, the threshold concentration being of the order of 0.1 to 0.3 mM. Spike-induced, phasic contractions showed a similar Ca⁺⁺-dependence. Variations in [Na⁺]₀ had only a slight and irregular influence on the Ca⁺⁺ dose-response curve of the depolarized muscles.Differences in the effects of Na⁺ on the rate of rise and the rate of fall of the contracture tension, respectively, suggested that Na⁺ is more important for the removal of Ca⁺⁺ from the contractile system than for the supply of Ca⁺⁺ to the system. With regard to the interaction of Ca⁺⁺ and Na⁺ in the excitation-contraction coupling the vascular smooth muscle seemed to differ from both heart muscle and skeletal muscle.The present study was supported by grants from the Swedish Medical Research Council (B 70-14x-28-06 A), from Air Force Office of Scientific Research through the European Office of Aerospace Research, OAR, United States Air Force under Contract F 1052-68-C-0044, from U.S. Public Health Service (HE-05678-08), from AB Hässle, Göteborg, and from the Deutsche Forschungsgemeinschaft (Bi 122/1).