Dimethylarginines in chronic renal failure

BACKGROUND: Nitric oxide (NO) is a potent chemical mediator involved in many functions. In vivo production of NO is thought to be regulated by endogenous analogues of L-arginine: asymmetric dimethylarginine (ADMA). AIM: To examine the effect of renal function and dialysis on the serum concentrations of ADMA and symmetric dimethylarginine (SDMA). METHODS: Blood samples were obtained from nine healthy subjects, patients with renal failure before (n = 17) and after haemodialysis (n = 9), nine patients on chronic ambulatory peritoneal dialysis (CAPD), and 13 patients with chronic renal failure on conservative treatment. Serum samples were extracted using a solid phase cation exchange column and the extracts were analysed by high performance liquid chromatography (HPLC). RESULTS: Serum concentrations of ADMA in patients with renal failure (mean, 1.04 micromol/litre; SD, 0.17) were significantly higher than those of controls (mean, 0.61 micromol/litre; SD, 0.13). Haemodialysis significantly decreased the serum concentration by 36% (before dialysis: mean 0.99 (SD, 0.25) micromol/litre; after dialysis: mean, 0.63 (SD, 0.15) micromol/litre). Serum SDMA concentrations were higher in patients with renal failure, and haemodialysis decreased the concentration by 60%. There was no difference in serum arginine concentrations between the groups. CONCLUSION: Serum concentrations of ADMA are increased in renal failure and haemodialysis reduces the concentration.     

Leachability of a new plasticizer tri-(2-ethylhexyl)-trimellitate from haemodialysis tubing

In two groups of patients on chronic haemodialysis treatment, the common PVC-DEHP blood tubing was replaced with tubing containing tri-(2-ethylhexyl)-trimellate (TOTM) as plasticizer. The aim of the present study was to measure the amount of TOTM and/or its metabolites (TAE s) in plasma, resulting from TOTM that might leach from the dialysis tubes. The arterial levels of TAE s at the start of the dialysis sessions were monitored by Selected Ion Monitoring (SIM) analysis once a week for a period of 42 days. A gradual decrease in TAE was observed during the first 21 days of the haemodialysis treatment with the PVC-TOTM tubes. After three weeks, the TAE levels remained constant until the end of the study. On day 120 of the haemodialysis treatment, the plasma TAE concentrations from the inflow and outflow tubes of the dialyzer were monitored during a single haemodialysis session at different times after starting dialysis. At the beginning of the dialysis session, the mean concentration of TAE was 55.81 +/- 14.98 ng/ml (mean +/- standard error), while at the end the levels were 73.34 +/- 17.05 ng/ml. There were no significant differences between venous and arterial sampling points in the trimellitic ester concentrations. Less TOTM is apparently leached from haemodialysis than DEHP. TOTM can be recommended as an alternative plasticizer to DEHP, but its possible toxicity in humans should be investigated before it can be used routinely.     

Neurohumoral responses to a single haemodialysis in chronic renal patients

The effect of volume reduction on vasoactive substances and their role in estimating dry weight in haemodialysis patients was studied. Plasma atrial natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity and serum aldosterone were measured in 12 patients before and after bicarbonate haemodialysis. Haemodynamical changes were registered and cardiac function and diameter of the inferior vena cava were measured by echocardiography before and after dialysis. Plasma concentration of ANP was significantly reduced by haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas concentrations of the other hormones were unchanged. The change in the concentration of ANP did not have significant correlation with weight reduction. The concentration of ANP correlated positively with the diameter of the inferior vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The concentration of ANP before or after haemodialysis or its change during dialysis did not correlate with any other biochemical parameter. The results show that plasma ANP level is decreased after volume reduction in patients with chronic renal failure, whereas other hormonal systems are unresponsive. However, plasma concentration of ANP seems to have no role in estimating dry weight in chronic haemodialysis patients.     

Plasma concentrations of nitrate during the menstrual cycle, ovarian stimulation and ovarian hyperstimulation syndrome.

BACKGROUND: Nitric oxide (NO) is predominantly a locally acting mediator, affecting several functions in the human female reproductive tract. In vivo, it is quickly metabolized to its stable end product nitrate, which is cleared by the kidney. METHODS AND RESULTS: The aim of the present study was to evaluate possible fluctuations of plasma nitrate concentrations during the menstrual cycle, ovarian stimulation as well as ovarian hyperstimulation syndrome (OHSS). During the menstrual cycle (n = 19 women) the mean nitrate concentrations were between 26.7 and 29.5 micromol/l at all stages except for the day of ovulation, when the concentrations were significantly (P < 0.001) increased (mean 37.2 micromol/l +/- 2.0). Significantly lower concentrations of plasma nitrate (P < 0.01) were measured at the end of gonadotrophin-releasing hormone (GnRH) down-regulation (24.6 micromol/l +/- 1.4) compared with the concentrations found at day 8 of follicle-stimulating hormone (FSH) stimulation (34.9 micromol/l +/- 2.6) and at the day of human chorionic gonadotrophin (HCG) (35.6 micromol/l +/- 3.3). The concentrations of nitrate (33.4 micromol/l +/- 3.4) in women with OHSS (n = 13) were similar to those seen 5 days after embryo transfer (33.2 micromol/l +/- 2.3). CONCLUSIONS: The results indicate that NO synthesis is increased at the time of spontaneous ovulation. GnRH treatment inhibits NO synthesis, while NO production is not increased in women with OHSS.     

Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects

This study compared the effects of short-term creatine supplementation on muscle phosphocreatine, blood and urine creatine levels, and urine creatinine levels in elderly and young subjects. Eight young (24 +/- 1.4 years) and seven old (70 +/- 2.9 years) men ingested creatine (20 g day-1) for 5 days. Baseline muscle phosphocreatine measurements were taken pre- and post-supplementation using nuclear magnetic resonance spectroscopy (NMR). On the first day of supplementation subjects had blood samples taken immediately before and hourly for 5 h following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine levels was conducted. Twenty-four hour urine collections were conducted for 2 days prior to the supplementation period and for 5 days during supplementation. Old subjects had significantly higher baseline plasma creatine levels than young subjects (68.5 +/- 12.5 vs. 34.9 +/- 4.7 micromol L-1; P < 0.02). There were no significant differences between groups in plasma creatine pharmacokinetic parameters (i.e. area under the curve, elimination rate constant, absorption rate constant, time to maximum concentration, and maximum concentration) following the 5 g oral creatine bolus. Urine creatine, assessed pre and on 5 days of supplementation, increased (P < 0.001), with no difference between groups. Urine creatinine did not change as a result of creatine supplementation. Young subjects showed a significantly greater increase in muscle phosphocreatine compared with old subjects, and post-supplementation muscle phosphocreatine levels were greater in young subjects (young 27.6 +/- 0.5; old 25.7 +/- 0.8 mmol kg-1 ww) (P=0.02). There were no differences in blood or urine creatine between groups in response to supplementation, but old subjects had a relatively small increase (young 35% vs. old 7%) in muscle phosphocreatine after supplementation.     

Decreased levels of coenzyme Q(10) in patients with bronchial asthma

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive therapy in complex management of disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, and beta-carotene both in plasma and whole blood, and malondialdehyde (MDA) and eosinophil cationic protein (ECP) in plasma of asthmatics (As). METHODS: Fifty-six As (15 males and 41 females) aged from 19 to 72 years (mean age 46 years) suffering from allergic asthma were enrolled into the study. The control group comprised 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: The concentrations of CoQ10 decreased significantly both in plasma and whole blood, compared with healthy volunteers (0.34 +/- 0.15 micromol/l vs. 0.52 +/- 0.15 micromol/l, 0.33 +/- 0.14 micromol/l vs. 0.50 +/- 0.13 micromol/l, P < 0.001, P< 0.001, respectively). The levels of alpha-tocopherol were decreased both in plasma and whole blood in comparison with controls [24.10 micromol/l (19.8; 30.5), vs. 33.20 micromol/l (28.25; 38.05), 17.22 +/- 6.45 micromol/l vs. 21.58 +/- 7.92 micromol/l, P= 0.006, P = 0.01, respectively]. The levels of MDA were elevated over the reference range in both groups (reference range < 4.5 micromol/l). No changes were seen in beta-carotene concentrations. Positive correlation was found between whole blood CoQ10 and alpha-tocopherol concentrations. CONCLUSION: Results of the study suggest a possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide a rationale for its supplementation.     

An 18oxygen inhalation method for determination of total body formation of nitric oxide in humans.

The formation of nitric oxide (NO) and the subsequent conversion of the NO formed into nitrate require molecular oxygen. Based on this fact, we have recently developed a method using inhalation of the stable oxygen isotope, i.e. 18O2, to determine total formation of NO in small laboratory animals. The method has now been further developed to be applicable also in humans. Five healthy awake male subjects inhaled a gas mixture of unlabelled and 18-labelled oxygen (approximate ratio 4:1) in nitrogen from a closed breathing system equipped with eliminators for carbon dioxide and water vapour. The ratio of unlabelled to 18-labelled oxygen, as well as the total oxygen concentration during the inhalation, were monitored. Venous blood samples were taken before and after the inhalation for analysis of unlabelled and 18O-labelled nitrate by gas chromatography/mass spectrometry. The procedure was repeated with the same protocol on a later occasion, during ongoing treatment with the NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA). The average nitrate level in plasma in the absence of L-NMMA was 26 micromol l-1. The rate of total synthesis of NO was estimated to be 0.38 +/- 0.06 mu mol kg-1 h-1, corresponding to a total body formation of 600-700 mu mol/24 h in an adult male. Infusion of L-NMMA caused an increase in mean arterial blood pressure from 86 +/- 4 to 99 +/- 5 mmHg (P<0.05). The average plasma level of nitrate during infusion of L-NMMA was 24 mu mol l-1. NO formation during infusion of L-NMMA was 0.17 +/- 0.03 mu mol kg-1 h-1, i.e. significantly (P<0.05) lower than in the absence of L-NMMA. We suggest that the described method allows direct determination of total NO formation in man. The method may be useful in the study of various experimental and pathophysiological conditions affecting NO formation.     

No role of interstitial adenosine in insulin-mediated vasodilation.

The mechanisms behind the vasodilatory effect of insulin are not fully understood, but nitric oxide plays an important role. We have investigated the possibility that insulin mediates vasodilatation in the human skeletal muscle via an increase in extracellular adenosine concentrations. In eight healthy subjects (H) and in four subjects with a complete, high (C5-C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min-1 kg-1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 +/- 25 and 318 +/- 18 mL min-1 to 451 +/- 41 and 530 +/- 29 mL min-1, SCI and H, respectively [mean +/- SEM]). Concentrations of adenosine in the muscle ECF did not change with infusion of insulin and did not differ between groups (before: 147 +/- 55 [SCI] and 207 +/- 108 [H] nmol L-1; during: 160 +/- 36 [SCI] and 165 +/- 74 [H] nmol L-1). No significant correlation between concentrations of adenosine and corresponding LBF rates was achieved (LBF=[-0.0936. Adenosine] + 475. R=-0.092, P=0.22, number of samples=181, number of subjects=12). Conclusion: the mechanism by which insulin mediates an increase in skeletal muscle blood flow is not associated with adenosine in the ECF.     

Calcitonin gene-related peptide (CGRP) and leg vascular resistance during head-up tilt induced hypovolaemic shock in man

Calcitonin gene-related peptide is a potent vasodilator and its distribution in perivascular nerves suggests a role in the regulation of vascular tone. We evaluated leg vascular resistance together with total peripheral resistance and the arterial plasma concentrations of calcitonin gene-related peptide and catecholamines during 50 degrees head-up tilt induced hypotension in 7 males. During tilt mean arterial pressure, heart rate, total peripheral resistance, leg vascular resistance and plasma noradrenaline increased, while cardiac output and leg blood flow decreased. After 45 +/- 9 min (mean +/- SE) presyncopal symptoms appeared together with decreases in mean arterial pressure (81 +/- 6 to 56 +/- 9 mmHg), heart rate (97 +/- 6 to 73 +/- 8 beats min-1), leg vascular resistance (158 +/- 9 to 109 +/- 8 mmHg min l-1) and total peripheral resistance (17 +/- 3 to 10 +/- 2 mmHg min l-1) (P less than 0.01). Plasma calcitonin gene-related peptide increased from 32 +/- 3 to 35 +/- 3 pmol l-1 (P less than 0.01) and adrenaline from 1.1 +/- 0.2 to 1.7 +/- 0.3 nmol l-1 (P less than 0.01), while noradrenaline did not change. The results indicate that presyncopal symptoms induced by head-up tilt are associated with regional as well as total decreases in vascular resistance accompanied by moderate increases in arterial plasma concentrations of calcitonin gene-related peptide and adrenaline.     

Seminal plasma nitrite/nitrate and intratesticular Doppler flow in fertile and infertile subjects

The objective of the present study was prospectively to evaluate the role of nitric oxide (NO) in modulating intratesticular blood flow and sperm function. A total of 56 males, undergoing assisted reproduction, were divided into three groups according to semen analysis: (i) normozoospermic (n = 16); (ii) oligozoospermic (n = 21); and (iii) azoospermic (n = 19). All the subjects were submitted to hormone analysis [luteinizing hormone, follicle stimulating hormone (FSH), growth hormone, testosterone, androstenedione, insulin], and to ultrasonographic (testicular volume) and Doppler (transmediastinal artery) evaluations. Plasma and seminal plasma nitrite/nitrate concentrations, and plasma insulin-like growth factor-I were assayed. All 56 patients completed the study. In normozoospermic patients, significantly greater testicular volume, lower transmediastinal resistances, and higher seminal plasma nitrite/nitrate concentrations were observed in comparison with both oligo- and azoospermic subjects. Testicular volume was inversely correlated with plasma FSH (r = -0.589; P = 0.005) and pulsatility index of transmediastinal artery (r = -0.402; P = 0.049). Furthermore, the seminal plasma nitrite/nitrate concentrations were inversely correlated with pulsatility index of transmediastinal artery (r = -0.511; P = 0.015). It was concluded that NO is involved in vascular modulation of testicular vessels and ultimately in sperm output.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of alpha-adrenoceptor antagonists

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an alpha-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H2 technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n = 10); yohimbine-treated (200 micrograms . kg-1 . h-1, n = 7); and prazosin-treated (50 micrograms . kg-1 . h-1, n = 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102 +/- 1 mmHg (mean +/- SE) to approximately 50 +/- 1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109 +/- 12 ml . 100 g-1 . min-1) compared to the control group (69 +/- 6 ml . min-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 +/- 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by alpha 2-adrenoceptors in the feline cerebrovascular bed.     

超滤曲线与钠曲线联合应用对透析相关低血压的影响

目的探讨超滤曲线与钠曲线联合应用对血液透析相关低血压的影响。方法20例维持性血液透析易发生低血压患者,其中男性9例,女性11例;年龄25—68岁,平均年龄44岁;体质量46．0～72．5kg,平均体质量59．9kg。随机分为试验组和对照组,每组10例（试验组男：女为4：6;对照组男：女为5：5）。分别给予超滤曲线与钠曲线结合透析（试验组）和标准模式透析（对照组）1个月（共12次）,比较两组患者透析前血压、透析过程中血压及低血压的发生率、透析前后血清钠浓度。结果试验组与对照组超滤量及透析间期体质量增长差异无统计学意义（P〉0．05）;两组之间透析前及透析1h、透析2h血压变化差异无统计学意义（P〉0．05）,试验组在透析3h、透析4h血压高于对照组,差异有统计学意义（P〈0．05）;透析过程中,试验组低血压发生率17％,对照组为41％,差异有显著统计学意义（P〈0．01）,透析4h,试验组和对照组血清钠浓度差异无统计学意义（P〉0．05）。结论超滤曲线与钠曲线结合透析可以有效预防透析相关低血压的发生,而对血清钠离子浓度无明显影响。     

Die sympathische Aktivität bei terminaler Niereninsuffizienz und Nierentransplantation

Summary Blood pressure as well as noradrenaline, creatinine and electrolytes in blood and urine were compared in normal controls (n=25), patients with chronic renal failure (n=39), patients with continuous ambulatory peritoneal dialysis (CAPD) (n=28) and haemodialysis patients before and after renal transplantation (n=63). The average blood pressures of the control group and the CAPD patients were lower than those of the renal failure patients without and with haemodialysis. After renal transplantation elevated blood pressure normalised in 18% within the following 6 months. In all groups of patients with renal failure the mean noradrenaline plasma concentration was increased more than three-fold of normal values: 1,470 pg/ml in patients with chronic renal failure, 1,366 pg/ml in CAPD patients and 1,284 pg/ml in patients with haemodialysis. No correlation was found between these elevated noradrenaline plasma levels and blood pressure. However, there was a significant correlation between noradrenaline excretion and sodium excretion. Compared to the controls, the urine excretion of noradrenaline was significantly lower in patients with chronic renal failure and almost zero in patients with dialysis treatment. Two days after renal transplantation the mean noradrenaline urine excretion increased to 15.7±1.8 µg/day and 4 days after transplantation the noradrenaline plasma concentration decreased to 592±155 pg/ml. Nine months after renal transplantation the creatinine clearance was 76 ml/min and the mean noradrenaline plasma concentration 438±153 pg/ml. It is concluded that in chronic renal failure the level of noradrenaline plasma concentration is dependant on renal function.

---

Abkürzungen CAPD continuous ambulatory peritoneal dialysis Zum 60. Geburtstag von Herrn Prof. Dr. W. Kaufmann     

Atrial natriuretic peptide during head-up tilt induced hypovolaemic shock in man

To evaluate the importance of right atrial filling pressure versus central blood volume for the plasma concentration of atrial natriuretic peptide in man, head-up tilt to 50 degrees maintained until the appearance of presyncopal symptoms was carried out in six healthy males. Head-up tilt increased thoracic electrical impedance from 35.4 +/- 0.9 (mean and SE) to 39.2 +/- 0.9 ohm, mean arterial pressure from 64.5 +/- 3.6 to 76.6 +/- 3.0 mmHg and heart rate from 51 +/- 3 to 85 +/- 4 beats min-1 (P less than 0.01). After 35 +/- 7 min presyncopal symptoms appeared, together with a decrease in mean arterial pressure to 51 +/- 4 mmHg and in heart rate to 59 +/- 7 beats min-1 (P less than 0.01). Central venous pressure (2.1 +/- 1.0 mmHg) did not change significantly, but atrial natriuretic peptide decreased from 9.4 +/- 1.6 to 4.2 +/- 1.3 pmol l-1 (P less than 0.01) and was inversely related to thoracic impedance (r = -0.65, n = 44, P less than 0.001). The results indicate that changes in the central blood volume rather than in central venous pressure determine the secretion of atrial natriuretic peptide in man.     

Loss of residual renal function in patients on regular haemodialysis

The literature offers scant data on loss of residual renal function in chronic haemodialysis patients. The present study was undertaken in 34 patients, to evaluate residual creatinine clearances (CCr) before the start of haemodialysis and after 3, 12 and 24 months. CCr progressively declined from 6.15 +/- 2.61 (before) to 1.40 +/- 1.29 ml.min-1 (after 24 months: p less than 0.01). The decrease was largest during the first three months of dialysis therapy (slope -0.99 +/- 1.01 ml.min-1.month-1 for the first three months vs. -0.23 +/- 0.12 ml.min-1.month-1 for the entire 24-month period: p less than 0.01). The decline in CCr during the first three months was significantly more pronounced in glomerular disease than in tubulo-interstitial disease (p less than 0.05). This could not be attributed to differences in blood pressure, body weight or hypotensive medications. Age and sex also had no influence. Our data indicate that there is a characteristic progressive loss of renal function in haemodialyzed patients and that the early decline is most pronounced in patients with glomerular disease. Regular assessment of residual renal function at least every three months is indicated in patients starting chronic haemodialysis treatment.     

Catecholamine response to the Wingate test in untrained women]

Supramaximal exercises are well known to induce a severe stress on the adrenal medulla and nervous sympathetic system. This stress induces increased plasma catecholamines concentrations. The responses of catecholamines to supramaximal exercises in women are still not well characterized and have been studied mostly in trained subjects. Hence the aim of the present study was to evaluate plasma catecholamine responses to a Wingate test in young and untrained women (n = 6) and men (n = 7). Venous plasma catecholamine concentrations were determined by HPLC, at rest, at the end of the warm-up and of the exercise, and during recovery (5, 10, 20, and 30 mn). Our results failed to show any significant difference in resting catecholamine concentrations ([A]p: 0.41 +/- 0.05 vs. 0.45 +/- 0.05 nmol. L-1; [NA]p: 3.28 +/- 0.68 vs. 2.58 +/- 0.26 nmol.L-1), kinetics, and maximal plasma catecholamine concentrations (Amax: 4.47 +/- 1.08 vs. 3.31 +/- 0.63 nmol.L-1; NAmax: 18.05 +/- 1.11 vs. 14.01 +/- 2.02 nmol.L-1) in response to the Wingate test between women and men, respectively. The Amax/NAmax ratio used as an index of adrenal medulla sensitivity to sympathetic input was also similar between genders. In conclusion, this study was able to demonstrate, in untrained subjects, that gender did not alder the sympatho-adrenergic response induced by a severe stress.     

Fluid balance in patients with chronic renal failure assessed with N-terminal proatrial natriuretic peptide, atrial natriuretic peptide and ultrasonography

The N-terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre-dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N-terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre-dialysis patients venous blood samples were taken during rest to measure plasma N-terminal proANP and ANP and serum creatinine. Normal values for N-terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N-terminal proANP and ANP in healthy volunteers were 328 +/- 92 and 11.4.0 +/- 3.1 pM L-1, respectively. In pre-dialysis patients, serum creatinine ranged from 110 to 447 microM L-1 and was significantly correlated to plasma N-terminal proANP (r = 0.60, P < 0.05) but not to ANP. This may indicate that N-terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N-terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N-terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N-terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N-terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.     

L-arginine transport at the fetal side of human placenta: effect of aspirin in pregnancy

L-Arginine transport by the fetal side of human placenta was investigated through the characterization of L-[3H]arginine uptake in isolated perfused cotyledon. Competitive inhibition experiments suggest the presence of at least two transport systems: a Na+-independent, pH-insensitive system inhibitable by cationic amino acids, similar to system y+, and a Na+-dependent system which recognizes both cationic and neutral amino acids only in the presence of Na+, i.e. a Bo,+-like system. The kinetic analysis of L-arginine uptake in the presence of Na+ revealed that the process is mediated by saturable components: a high-affinity system (Km = 167 +/- 18.0 microM; Vmax = 0.174 +/- 0.012 micromol min-1) and a low-affinity carrier (Km = 980 +/- 112 microM; Vmax = 1.60 +/- 0.12 micromol min-1). In the absence of Na+, L-arginine uptake was fitted by one model with a Michaelis-Menten constant of 200 +/- 24.8 microM. These results suggest that the high-affinity component corresponds to the Na+-independent system y+, whilst the low-affinity system may represent the activity of the Na+-dependent Bo,+ transporter. Kinetic studies in placentae taken from aspirin-treated pregnancies showed that L-arginine is transported with a significantly higher affinity (Km = 42.5 +/- 5.7 microM), but with a lower capacity (Vmax = 0.064 +/- 0.003 micromol min-1) than in the non-treated group. The latter finding suggests that aspirin would facilitate the uptake of the NO precursor only at very low arginine concentrations.     

Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance

We studied the relation of serum insulin levels to plasma lipid levels and blood pressure in two groups drawn from among 247 healthy, normotensive nonobese subjects with normal glucose tolerance. One group of 32 subjects was defined as having hyperinsulinemia (serum insulin, greater than 2 SD above the mean) and then compared with 32 normoinsulinemic subjects (serum insulin within 1 SD of the mean) matched for age (mean, 39 years), sex (22 men and 10 women), and body-mass index (24.7). The two groups had similar patterns of smoking, drinking, and physical exercise. Plasma glucose levels after an oral glucose challenge were significantly higher (P less than 0.05) in the hyperinsulinemic group. In addition, the mean (+/- SEM) fasting plasma triglyceride levels in subjects with hyperinsulinemia were significantly higher (1.73 +/- 0.2 vs. 1.24 +/- 0.1 mmol per liter) and the plasma high-density lipoprotein cholesterol concentrations were lower (1.21 +/- 0.06 vs. 1.43 +/- 0.06 mmol per liter) than in subjects with normoinsulinemia. Both systolic (126 vs. 119 mm Hg; P less than 0.05) and diastolic (85 vs. 78 mm Hg; P less than 0.01) blood pressures were significantly elevated in the group with hyperinsulinemia. We conclude that healthy persons with hyperinsulinemia and normal glucose tolerance have an increase in risk factors for coronary artery disease, as compared with a well-matched group of healthy subjects with normal insulin levels.     

Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure

BACKGROUND: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. METHODS: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. RESULTS: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). CONCLUSIONS: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.