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Hormones are specific molecules measured in biological fluids by elaborate analytical systems requiring meticulous attention. Variation between laboratories can be expected. However, recently published measurements of AVP, OXT, and BNP in human plasma under basal/control conditions include numbers which, between publications, vary by 100–10 000‐fold. Generally, the methods descriptions are scant, at best, and provide no information about quality control measures. Clearly, two results describing the same basal hormone concentration by numbers three orders of magnitude apart are incongruent providing reason for concern. Basal concentrations of bioactive AVP, OXT, and BNP in human plasma are in the order of 1–10 pmol/L. Therefore, assay systems applied to plasma must be able to measure concentrations of less than 1 pmol/L with appropriate specificity and accuracy. Basal concentrations of AVP, OXT, and BNP above 100 pmol/L should be reconsidered, as such results do not reflect bioactive hormone levels in humans, rats, or mice. Any concentration above 1000 pmol/L is of concern because such levels of bioactive hormone may be seen only under extreme conditions, if at all. [ABSTRACT FROM AUTHOR]

In the example in the figure, the excretion of the 60 mmol/d of H SP + sp is split between ammonia and phosphate buffering (58% to ammonia/ammonium ion and 42% to dihydrogen/hydrogen phosphate). The title of the I editorial i is 'Strong ion difference in urine: A measure of renal proton excretion or of the net plasma charge alteration? 4 Alevrakis E, Gialelis N, Vasileiadis I. Strong ion difference in urine: A measure of proton excretion or of the net plasma charge alteration?. [Extracted from the article]

Replicability of experimental results and optimal use of experimental animals are everybody's concern. Current efforts towards increased replicability include guidelines and checklists as tools for experimenters, referees, editors and publishers. Guidelines are also provided for appropriate use of animals. To ensure the quality of experimental results, the number of animals must be adequate, that is, sufficiently large, for the purpose of the given experiment. To comply with current ethical recommendations, the use of animals should be reduced as much as possible. Therefore, determination of the number of animals for a given scientific objective includes contrasting considerations. Current guidelines for animal experimentation, notably from the National Institute of Health, mandate (with very few exceptions) inclusion of animals of both sexes in experimental designs statistically powered to address the difference between the two groups. Notably, absence of evidence for sex differences between the organ or system functions under study does not qualify as an exception. Mandatory, equal representation of both sexes raises several questions including ethical ones. Other guidelines, by public regulators and major publishers, do not seem to have a similar selective focus on sex differences. In summary, current concerns about replicability of scientific results are justified. Concomitantly, the knowledge of sex differences also between non‐reproductive, non‐endocrine organ functions is increasing. In principle, sex matters in any experimental context. However, an indiscriminate demand for inclusion of both sexes in all experimental protocols seems a waste of animals, money and time, violating traditional principles of animal experimentation, particularly that of reduction. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE In rodents, the endothelial KCa channels, KCa3.1 and KCa2.3, have been shown to play a crucial role in initiating endothelium-derived hyperpolarizing factor (EDHF) vasodilator responses. However, it is not known to what extent these channels are involved in blood pressure regulation in large mammals, which would also allow us to address safety issues. We therefore characterized canine endothelial KCa3.1 and KCa2.3 functions and evaluated the effect of the KCa3.1/KCa2.3 activator SKA-31 on blood pressure and heart rate in dogs. EXPERIMENTAL APPROACH Canine endothelial KCa3.1/KCa2.3 functions were studied by patch-clamp electrophysiology and wire myography in mesenteric arteries. Systemic cardiovascular actions of acute SKA-31 administration were monitored in conscious, unstressed beagle dogs. KEY RESULTS Mesenteric endothelial cells expressed functional KCa3.1 and KCa2.3 channels that were strongly activated by SKA-31. SKA-31 hyperpolarized the endothelial membrane and doubled endothelial hyperpolarization-dependent vasodilator responses in mesenteric arteries. SKA-31 (2 mg·kg−1, i.v.) rapidly decreased the MAP by 28 ± 6 mmHg; this response was transient (8 ± 1 s), and the initial drop was followed by a fast and pronounced increase in HR (+109 ± 7 beats min−1) reflecting baroreceptor activation. SKA-31 significantly augmented similar transient depressor responses elicited by ACh (20 ng·kg−1) and doubled the magnitude of the response over time. CONCLUSIONS AND IMPLICATIONS Activation of endothelial KCa3.1 and KCa2.3 lowers arterial blood pressure in dogs by an immediate electrical vasodilator mechanism. The results support the concept that pharmacological activation of these channels may represent a potential unique endothelium-specific antihypertensive therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO x) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear. Aims: The aims of the present study were to measure changes in exhaled NO in relation to circulating NO x, RAAS, and haemodynamics. Methods: Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO x and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (DLCO). Eight matched healthy individuals served as controls. Results: All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and DLCO. NO x concentrations were not significantly increased in the patients. NO x correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations. Conclusion: In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO x do not seem to reflect pulmonary and systemic NO release, but NO x seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis. [ABSTRACT FROM AUTHOR]

1. Herein, we review mechanisms of sodium balance operating at constant mean arterial blood pressure (MABP); that is, under conditions where MABP does not provide the primary signal to the kidney. 2. Relative constancy of body fluids requires accurate regulation of total body sodium (TBS). Normally, plenty of sodium is ingested and balance is achieved by control of renal excretion driven by multiple central nervous, cardiovascular, endocrine and renal tubular mechanisms. Subtle changes in sodium balance are associated with parallel changes in extracellular volume (due to fast and precise osmoregulation), but not necessarily in MABP. Therefore, signals other than MABP seem to be the primary link between TBS and kidney function. 3. Renal functions involved in sodium homeostasis include: (i) the rate of glomerular filtration (GFR) determined by renal haemodynamics, including tubuloglomerular feedback (TGF); (ii) proximal tubular reabsorption involving glomerulotubular balance (GTB) and neurohumoral control; (iii) macula densa mechanisms influencing TGF and renin secretion; and (iv) distal tubular reabsorption dominated by the renin–angiotensin–aldosterone system (RAAS). 4. The present review focuses on the interactive, homeostatic operation of TBS, MABP, GTB, TGF and the RAAS. Regulation of sodium balance involves neurohumoral control of tubular sodium reabsorption, including proximal reabsorption. Central nervous system-mediated regulation of the latter modulates renin secretion. Homeostatically, the RAAS–TGF interaction seems analogous to a spring–shock absorber set-up: non-adaptive RAAS functions determine the new steady state position, whereas TGF controls the rate of change. Recruitment of renin-secreting cells during sustained stimulation may be essential for chronic adaptation, although details of this afferent arteriolar cell plasticity are unclear at present. [ABSTRACT FROM AUTHOR]

Abstract: Background: Natriuretic peptides and Tei index are useful indices for risk stratification in advanced left ventricular dysfunction (LVD). Their role in early stages is less clear. Aims: In relation to first diagnosis of LVD to assess the relation of plasma B-type-natriuretic peptide (NT-proBNP) with Tei index, assess serial changes in indices, and to assess the value of indices to predict functional status. Methods: Doppler echocardiography and neurohormonal analysis were performed (n =150). NYHA class was registered. Results: Tei index correlated with p-NT-proBNP (r =0.75, p <0.0001), and changes in indices correlated (r =0.36, p =0.001) in LVD (n =80). No functional improvement (n =47) was related to a median increase in Tei index (−0.2, −0.16; 0.09); an improvement (n =31) to a reduction (0.06; −0.19; 0.35), p =0.02. In the group with functional improvement, more patients had ≥30% reduction in p-NT-proBNP (75% vs. 45%, p <0.01). Addition of NT-proBNP or Tei index to a clinical model, of no functional improvement, improved log-likelihood χ 2 from 9.32 to 20.18 (p =0.001) and 20.67 (p =0.001). Conclusion: Tei index and p-NT-proBNP demonstrated a fair correlation. Unimproved NYHA class was related to progressive LVD and might be identified by monitoring Tei index or p-NT-proBNP. Advanced LVD and high pre-treatment p-NT-proBNP levels indicated a potential of improvement in functional status. [Copyright &y& Elsevier]

Background: The use of anthracyclines in treatment of cancer is limited by cardiotoxicity of these compounds and may lead to heart failure. Therefore monitoring of cardiac function is necessary during therapy. Aim: We evaluated the value of natriuretic peptides (N-terminal pro-atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP)) for monitoring and predicting anthracycline induced cardiotoxicity using radionuclide left ventricular ejection fraction (EF) measurements as reference. Methods and results: A total of 107 consecutive patients receiving anthracycline as part of their chemotherapy for malignant disease were studied. Plasma concentrations of the peptides were measured by radioimmunoassay and EF by radionuclide cardiography. For reduced EF values, i.e. below 0.50 a fairly strong correlation was found between N-ANP or BNP and EF. Of 48 patients with serial EF and peptide measurements, 19% showed a significant EF decrease (>0.10) and ended with a final EF value below 0.50. Baseline EF was no predictor of a change in EF during treatment. Neither baseline levels of N-ANP or BNP nor a change in the same variables during therapy were predictive of a change in EF. Conclusions: In spite of correlations between peptide concentrations and reduced EF values neither baseline values nor serial measurements can safely substitute EF monitoring in patients undergoing anthracycline therapy. [Copyright &y& Elsevier]

The study was designed to determine to what extent moderate elevation of renal perfusion pressure (RPP) via the mechanism of 'pressure natriuresis' contributes to the natriuresis induced by acute i.v. saline loading. Nine Beagle dogs maintained on ample sodium intake (5.5 mmol (kg body mass)-1 day-1) were chronically equipped with an aortic occluder to servocontrol RPP, a bladder catheter to measure renal function, and catheters for measurement of RPP and mean arterial blood pressure (MABP). A swivel system allowed free movement in the kennel during experiments. Isotonic saline loading (500 ml in 100 min) was studied as follows: with and without servocontrol of RPP, and these two protocols repeated in the presence of angiotensin-converting enzyme inhibition (ACEI, Enalapril, 2 mg (kg body mass)-1). Saline loading increased MABP by about 12 mmHg and sodium excretion from about 28 µmol min-1 up to about 350 µmol min-1. Without ACEI, servocontrol of RPP at 10% below control 24h MABP slightly delayed the onset of the saline-induced natriuresis, but did not reduce peak sodium excretion or cumulative sodium excretion. The slight delay most probably resulted from pressure-controlled renin release because, with ACEI, servocontrol of RPP did not delay or reduce the saline-induced natriuresis. In conclusion, pressure natriuresis does not contribute to the natriuresis following acute saline loading. [ABSTRACT FROM AUTHOR]

Aims: In patients with essential hypertension, abnormal renal sodium handling includes exaggerated natriuresis in response to extracellular volume expansion. We tested the hypothesis that exaggerated natriuresis is associated with increases in medullary and/or cortical renal blood flow. Methods: Patients with mild essential hypertension, but no signs of end organ damage, and control subjects were studied after 4 days of dietary standardization (<60 mmol Na+ day−1) preceded in patients by a 14‐day drug washout period. On the study day, subjects received a 4‐hour intravenous volume expansion with saline (2.1% of body mass). Renal medullary and cortical blood flows were measured by PET scanning using H215O as tracer; anatomical regions of interest were defined by contrast‐enhanced CT scanning. Results: In patients, arterial blood pressure increased during volume expansion (107 ± 2‐114 ± 3 mm Hg, P < 0.05) in contrast to the control group (92 ± 2‐92 ± 2 mm Hg). Renal sodium excretion increased more in patients than in controls (+133 ± 31 µmol min−1 vs +61 ± 14 µmol min−1, respectively, P < 0.05) confirming exaggerated natriuresis. During volume expansion, renal medullary blood flow did not change significantly in patients (2.8 ± 0.4‐2.5 ± 0.5 mL (g tissue)−1 min−1) or in controls (3.2 ± 0.3‐3.1 ± 0.2 mL (g tissue)−1 min−1). In control subjects, renal cortical blood flow fell during volume expansion (4.1 ± 0.3‐3.7 ± 0.2 mL (g tissue)−1 min−1, P < 0.05) in contrast to patients in which deviations remained insignificant. Conclusion: Exaggerated natriuresis, a hallmark of essential hypertension, is not mediated by increases in regional, renal blood flow. [ABSTRACT FROM AUTHOR]

Presents an introduction to the September 2005 issue of the journal "Acta Physiologica Scandinavica."

The guest editor discusses several articles published within this issue including one by Denis Burdakov on glucose-inhibited neurons, and another by Javier Garcia-Sancho on how the use of targeted aequorins can give information about Ca2+ signal modulation by various organelles.

When injected as a bolus into the circulation of isolated, perfused kidneys or into anesthetised rats, Up4A elicits vasoconstriction (Jankowski V. et al. Nature Med. 11:223, 2005). We have investigated the cardiorenal effects of intravenous infusion of Up4A in conscious rats provided with chronic catheters in both femoral vessels and the bladder. The rats were trained to stay in a plastic retainer for the duration of the experiment. Up4A in isotonic glucose was given as step-up infusion at rates of 8 - 32 and 128 nmol/min per kg body mass for 30 rain per rate. The lower doses had no effect on mean blood pressure, heart rate or renal functions. The highest dose caused a small, but highly consistent decrease in arterial pressure (114±3 to 108±3 mmHg, p<0.001, n=6) together with an increase in heart rate (461±17 to 489±13 bpm, p<0.001); both rebounded immediately after the infusion to 119±3 mmHg and 436±20 bpm, respectively. Concomitantly, sodium excretion decreased by >75% (1.11±0.52 to 0.24±0.07 µmol/min, p<0.05), and potassium excretion fell by some 60% (1.85±0.62 to 0.65±15 µmol/min, p<0.05). Urine flow was not significantly affected. It is concluded that in the conscious rat, a step-up infusion of Up4A causes vasodilatation and electrolyte retention. [ABSTRACT FROM AUTHOR]