Interaction of epicutaneously applied lipids with stratum corneum depends on the presence of either emulsifiers or hydrogenated phosphatidylcholine.

The barrier function of the stratum corneum (SC) significantly determines the interaction of epicutaneously applied substances with the skin organ. Although the exact molecular processes are still unclear, it is undoubted that the intercellular lipid composition and order of the SC is significantly involved in this interaction. Topically substituted phases, especially those of lipophilic composition, seem to interact very intensely with lipid membranes; they can be integrated, form separate phases, or even permeate through the SC into the viable skin. The latter is not desired, especially in barrier-protective preparations with a lipophilic phase. The present paper investigates the penetration behavior of topically applied, DiI-labeled lipids into human ex vivo skin depending on the phase organization of different o/w emulsifiers compared to emulsifier-free preparations containing hydrogenated phosphatidylcholine by means of fluorescence indication. Results are presented for intact and defined damaged epidermal barrier. In addition, the washout effect based on skin samples treated by artificial watering after lipid incubation, and the influence of the phase transition temperature of the SC membrane were studied. The results show that in intact and damaged skin, the penetration depth of the lipids increases directly proportionally with the hydrophilic-lipophilic balance (HLB value), while the washout effect and the HLB value proved to be inversely related. An increase in penetration depth with higher HLB values was also apparent when the phase transition temperature of the physiological membranes was exceeded. Altogether, the results clearly demonstrate that the characteristics of the emulsifying phase of a preparation significantly determine the interaction of a substituted lipophilic phase with the SC. Especially bipolar lipids, like phosphatidylcholines, showed intradermal dispersion patterns which hint at an especially intense interaction with physiological membranes.

Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study).

BACKGROUND: For long-term management of atopic eczema, the use of skin care creams is recommended, but effectiveness of this treatment is not well established. OBJECTIVE: The objective of this study was to yield data on the skin care properties of a cream with a unique lamellar matrix containing N-palmitoylethanolamine (PEA) and to assess quality-of-life variables in patients with mild to moderate atopic eczema. SETTING: In this multinational, multicentre, observational, non-controlled, prospective cohort study, patients between 2 and 70 years of age were enrolled. All patients were supplied with the study product sufficient for treatment over the entire study period. Outcome was followed in periods between 3 and 7 days and 4 and 6 weeks after study start. Data were gathered from doctor reports and patient self-assessments via patient questionnaires. RESULTS: Data from 2456 patients entered the database. The mean examination intervals were 6 days for the 3- to 7-day period and 38 days for the 4- to 6-week period. At study end, intensities of erythema, pruritus, excoriation, scaling, lichenification and dryness were significantly reduced with a combined score reduction of 58.6% in the entire population (57.7% in adults > 12 years and 60.5% in children

[Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus]. / Topische Cannabinoidagonisten. Eine effektive, neue Möglichkeit zur Behandlung von chronischem Pruritus.

BACKGROUND: Chronic, therapy-resistant pruritus often fails to respond to standard measures so new therapeutic approaches are needed. Recently, the expression of cannabinoid receptors on cutaneous sensory nerve fibers was described, so cannabinoid agonists seem a rational therapeutic option for pruritus. PATIENTS: In an open application observation 22 patients with prurigo, lichen simplex and pruritus applied an emollient cream containing N-palmitoyl ethanolamine (PEA). RESULTS: In 14/22 patients a good antipruritic effect could be documented. The average reduction in itch was 86.4%. The therapy was well-tolerated by all patients; neither burning burn nor contact dermatitis was observed. CONCLUSIONS: Topical cannabinoid agonists represent an new effective and well-tolerated therapy for refractory itching of various origins. Creams with a higher concentration may be even more effective with broader indications.

Contribution of pressure natriuresis to control of total body sodium: balance studies in freely moving dogs.

1. This study aims at determining whether elevation of renal perfusion pressure (RPP) may correct for increased total body sodium (TBS), via pressure natriuresis. 2. Freely moving dogs were studied on four consecutive days. During day 1, low-dose angiotensin II and aldosterone were infused. Pressure natriuresis was prevented by servo-controlling RPP to 20 % below the control level. Sodium and water retention increased TBS and total body water. Mean arterial blood pressure rose by approximately 25 mmHg. 3. In protocol 1, infusions and control of RPP were maintained over three more days. Sodium was retained on all days, resulting in a continuous increase in TBS. 4. In protocol 2, control of RPP was stopped after day 1. Thus, pressure natriuresis could exert its effect beginning with day 2. Angiotensin II and aldosterone infusions were continued. This prevented the effects of endogenous suppression of the renin-angiotensin-aldosterone system (RAAS), which is caused by increased TBS. No further sodium retention occurred, i.e. TBS remained at the elevated level gained on day 1. 5. In protocol 3, control of RPP and the infusions were stopped. Thus, pressure natriuresis and RAAS suppression could exert their combined effects. Sodium excretion exceeded sodium intake on day 2. Control level of TBS was regained within 24 h. 6. It was concluded that when RPP is considerably elevated, pressure natriuresis prevents further increase of TBS in the face of elevated angiotensin II and aldosterone levels. However, pressure natriuresis does not suffice to restore TBS to control. This requires additional endogenous suppression of RAAS.

Antihypertensive effect of 0.1-Hz blood pressure oscillations to the kidney.

BACKGROUND: Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. METHODS AND RESULTS: Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. CONCLUSIONS: BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Pressure-dependent renin release: effects of sodium intake and changes of total body sodium.

The impact of sodium intake and changes in total body sodium (TBS) for the setting of pressure-dependent renin release (PDRR) was studied in freely moving dogs. An aortic cuff allowed servo control of renal perfusion pressure (RPP) at preset values. Protocols were 1) high sodium intake (HSI), 2) low sodium intake (LSI), 3) TBS moderately increased (+3.1 mmol Na/kg body wt) by 20% reduction of RPP for 2-4 days, 4) large increase of TBS (+8.2) by combining protocol 3 with aldosterone infusion, and 5) TBS reduced (-3.1) by peritoneal dialyses. Twenty-four-hour time courses of arterial plasma renin activity (PRA) revealed that LSI increased PRA for the first 10 h only; afterward PRA did not differ between LSI and HSI. Reduced TBS increased PRA constantly, and the large increase of TBS constantly reduced PRA. PDRR stimulus-response curves (assessed 20 h after last sodium intake) revealed an exponential relationship in each protocol. PDRR was not changed by different sodium intake. Conversely, reduced TBS increased PDRR markedly, whereas the large increase of TBS suppressed it. Thus an inverse relationship between TBS and PRA, i.e., a TBS-dependent renin release, was found. This relationship was enhanced by decreasing RPP. This interplay between TBS-dependent renin release and PDRR allows the organism a differentiated reaction to changes in TBS and arterial pressure.

Mechanisms compensating Na and water retention induced by long-term reduction of renal perfusion pressure.

Endogenous downregulation of plasma aldosterone (Aldo) concentration, despite increased plasma renin activity (PRA), has been suggested to compensate Na and water retention, which is induced by long-term reduction of renal perfusion pressure (rRPP). To determine whether fixed plasma Aldo concentration would prevent equilibration of 24-h Na and water balances during rRPP, chronically instrumented, freely moving beagle dogs were kept under standardized conditions (daily intake 5.5 mmol Na/kg body wt) and studied for 4 consecutive days under the following conditions: control without rRPP (protocol 1) and rRPP + infusion of Aldo (rRPP + Aldo, protocol 2). Because Aldo administration reduces PRA and, thereby, angiotensin II (ANG II) levels ANG II was additionally infused in protocol 3 (rRPP + ANG II + Aldo). During rRPP + Aldo, 24-h Na balances were never equilibrated. Daily Na retention was approximately 3.5 mmol/kg body wt on day 1 and decreased to approximately 1.6 mmol/kg body wt on day 4; 24-h water balances changed in a similar manner. PRA decreased stepwise. On all rRPP + ANG II + Aldo days, Na and water retentions were more extensive than during rRPP + Aldo. Daily Na retention decreased from approximately 4.4 mmol/kg body wt on day 1 to approximately 3.0 mmol/kg body wt on day 4. Plasma atrial natriuretic peptide increased during both protocols. It is concluded that 1) endogenous downregulation of components of the renin-angiotensin-aldosterone system is a pivotal compensatory mechanism to reduce Na and water retention and 2) natriuretic and diuretic factors seem to be of minor potency, because not even the sum of all could counterbalances the Na- and water-retaining effects of Aldo and ANG II.

Changes of blood pressure, sodium excretion and sodium balance due to variations of the renin-angiotensin-aldosterone system.

UNLABELLED: Studies were performed in partly free moving Beagle dogs, kept under standardized environmental and dietetic conditions (food intake: once daily at 8:30 a.m., 5.5 mmol Na/kg body weight per 24 h). The dogs were chronically instrumented with an inflatable cuff around the aorta above the renal arteries, two aortic catheters above and below the cuff, and a bladder catheter. Three protocols were performed in 7 dogs each: (i) CONTROL: urine collection in 20-min intervals and measurement of Na excretion, continuous registration of mean arterial blood pressure (MABP) and heart rate for 4 consecutive days. (ii) As (i), but additional servocontrolled reduction of the renal perfusion pressure (rRPP) to stimulate renin secretion and the formation of angiotensin II and aldosterone. (iii) As (ii), but additional constant infusion of the angiotensin converting enzyme inhibitor Captopril. Despite rRPP Na is only transiently retained (pressure escape). MABP level is elevated, as long as total-body Na is augmented. In protocol iii no Na retention occurs, indicating that rRPP per se causes no Na retention. MABP level remained unchanged. Independent of the preset MABP level similar diurnal variation in MABP are present in all protocols. During control days major amounts of Na are excreted postprandially. Up to 5:00 p.m. 65% of the daily Na intake is excreted. After disturbance of Na control (protocols ii and iii) the Na excretion is shifted to the evening and night. Probably due to this shift Na retention can be prevented. Furthermore, these results demonstrate that rRPP-induced increases of total body Na and MABP are solely mediated by the activation of the renin-angiotensin-aldosterone system.

Diurnal pattern of sodium excretion in dogs with and without chronically reduced renal perfusion pressure.

In 5 conscious dogs the diurnal patterns of urinary sodium excretion (UNaV) were investigated, initially during 1 control day and, thereafter, during 4 days of servo-controlled reduction of renal perfusion pressure (rRPP). The individual dog's mean arterial blood pressure was reduced to 80% of the blood pressure on the control day. This value was always found to be below the threshold for the pressure-dependent renin release. During the entire study period urine was collected in 4-hour intervals and blood samples were taken every 4 h. The dogs were kept on a standardized high sodium and high water intake and were fed once daily at 8.30 h. On the control day, UNaV, urinary flow rate (UV), fractional lithium excretion (FELi) and fractional sodium excretion (FENa) had similar diurnal patterns. They peaked 4-8 h after food intake and decreased to low values during the night. On day 1 of rRPP, UNaV and FENa were maintained at very low levels in all collection periods, whereas the patterns of UV and FELi were unaltered compared with the patterns on the control day. On days 2-4 of rRPP, a clear-cut maximum in the patterns of UNaV and FENa recurred, comparable with the patterns on the control day. However, compared with the control day this maximum was shifted by 4 h towards the night. In contrast, the patterns of UV and FELi remained unchanged compared with the control day. The results indicate that UNaV has a typical time course in conscious, sodium- and water-replete dogs fed once daily. Endogenous stimulation of sodium reabsorption by means of rRPP results in a characteristic 4-hour shift of UNaV and FENa towards the night during rRPP days 2-4. This delay in UNaV seems to be evoked by processes in the distal tubule.

ACE inhibition prevents Na and water retention and MABP increase during reduction of renal perfusion pressure.

Two groups of six dogs were studied during 4 control days and 4 days of reduced renal perfusion pressure (rRPP) servo controlled at 20% below the individual dog's 24-h mean arterial blood pressure (MABP) during control days, i.e., below the threshold for renin release. On rRPP days, endogenous activation of plasma aldosterone and angiotensin II was inhibited by the angiotensin-converting enzyme inhibitor captopril. The dogs were kept on a high-Na and high-water intake. Unlike studies during rRPP alone, there was no Na and water retention during rRPP+captopril. Glomerular filtration rate dropped by approximately 9%, and MABP remained in the range of control days. Plasma renin activity rose to values 14 times greater than control, whereas plasma aldosterone decreased by approximately 60%. Atrial natriuretic peptide remained in the range of controls. In conclusion, angiotensin-converting enzyme inhibition can prevent the otherwise obligatory Na and water retention and systemic MABP increase during a 20% reduction in renal perfusion pressure. This is achieved most likely via the captopril-induced fall in angiotensin II and plasma aldosterone levels.

Influence of captopril on 24-hour balances and the diurnal patterns of urinary output, blood pressure, aldosterone and atrial natriuretic peptide in conscious dogs.

The diurnal time course of urinary flow rate (UV), urinary sodium (UNaV), and potassium (UKV) excretion, and of hormones such as atrial natriuretic peptide (ANP) and aldosterone, was investigated during 5 days of continuous captopril infusion (15 micrograms.kg body weight-1.min-1) in 4 conscious dogs on a high sodium diet (14.5 mmol Na.kg body weight-1.24 h-1). All food and water was given once daily at 8.30 a.m. On the control day and on days 1, 3, and 5 of captopril infusion, urine was collected by an automated system at 20-min intervals over 24 h, blood was taken every 4 h. Mean arterial blood pressure (MABP) and heart rate were evaluated as 5-min averages. Time courses of UNaV, UV, and UKV were compared with the individual control day without captopril. With captopril, 24-hour balances for Na and H2O were slightly negative, while the K balance was slightly positive for 2-3 days. Thereafter, all 24-hour balances were restored. MABP continued to decrease even after Na and water intake and output had come into balance again. Captopril treatment changed the diurnal excretion pattern for UNaV and UV characteristically. In the postprandial period until 5 p.m., less Na and urine were excreted than on the control day, whereas during the evening and night more Na and urine were excreted. The changes in the excretion pattern persisted for the entire observation period. The results indicate that disturbances in the regulating systems, induced by converting-enzyme blockade, bring about complex reactions of, e.g., MABP, ANP and aldosterone that finally restore Na and water 24-hour input/output balances.

Endogenous variations and sodium intake-dependent components of diurnal sodium excretion patterns in dogs.

1. Automated, sequential, 20 min urine collections were made to provide a record of diurnal variations of urinary sodium excretion (UNaV) in seven dogs, in which the same daily intake of sodium, potassium and water was administered, at first orally (between 08.30 and 08.50 h) on day 1 and then by i.v. infusion at a constant rate on days 2 and 3. This basic protocol was employed for two different levels of sodium intake: normal (NSI; 2.5 mmol (kg body wt)-1 (24 h)-1) and high (HSI; 14.5 mmol (kg body wt)-1 (24 h)-1). 2. The aims were: firstly, to establish the diurnal pattern of UNaV under these circumstances; secondly, to find out whether the quantity of sodium administered influences this diurnal pattern; and thirdly, to distinguish endogenous fluctuations from intake-dependent components in the UNaV excretion patterns. 3. On day 1 (oral intake) all dogs exhibited a similar excretion pattern, which peaked between 13.00 and 15.00 h on both diets and then diminished again over the remainder of the 24 h period. 4. On days 2 and 3 (infusion) UNaV fluctuated within a considerable range. 5. On HSI, the maximal UNaV rates on day 1 were about double those observed on infusion days. On HSI, UNaV during infusion days seems to consist of a constant basal component of about 5-6 mumol (kg body wt)-1 min-1 upon which a fluctuating component is superimposed. The basal component may be a reactive homeostatic response to the high sodium intake, whereas the superimposed fluctuating component may reflect endogenous variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Resetting of 24-h sodium and water balance during 4 days of servo-controlled reduction of renal perfusion pressure.

This study examines whether an increase in renal perfusion pressure (RPP) is necessary to escape endogenously stimulated Na- and water-retaining mechanisms. In seven dogs stimulation was accomplished by a servo-controlled reduction of RPP (rRPP) below the threshold for pressure-dependent renin release for 4 days. Oral intake was standardized. Plasma renin activity (PRA) rose from 2.5 in controls to approximately 5 ng ANG I.ml-1 x h-1 during rRPP days. Plasma aldosterone concentration (PAC) increased by approximately 50% only on day 1 of rRPP but fell at or below control levels thereafter. The PAC-to-PRA ratio decreased during rRPP days. Atrial natriuretic factor (ANF) rose to values three times higher than in controls. Mean systemic blood pressure (MABP) rose from 111 +/- 12 in controls to 142 +/- 14 mmHg on day 4 of rRPP. On day 1 of rRPP 60% of the Na and 24% of the water intake were retained. However, after 2-3 days the input-output balance was restored but on a higher level of total body Na and total body water (new "set point"). Because elevated systemic MABP could not exert direct pressure effects on the kidneys due to servo control of rRPP, there must be other factors, e.g., fall in PAC, increase in ANF, and changes in intrarenal hemodynamics and physical factors that may have contributed to the resetting of input-output balances during rRPP.

ACE inhibition facilitates sodium and water excretion during PEEP in conscious volume-expanded dogs.

Increased activity of the renin-angiotensin system may be involved in sodium and water retention during controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP). We therefore evaluated renal, hemodynamic, and hormonal effects of an acute angiotensin-converting enzyme inhibition (ACEI) during PEEP and extracellular volume expansion in five trained chronically tracheotomized dogs. Three protocols were performed: control, 4 h spontaneous breathing with continuous positive mean airway pressure (Paw) of 4 cmH2O (CPAP 4); CMV 20, CPAP for 1st h, CMV with 20 cmH2O Paw for 2 h (2nd and 3rd h), and 1 h of CPAP (4th h); and CMV20-ACEI, ACEI (Ramipril, 2 mg/kg body wt) followed by the same protocol as in CMV 20. During control, sodium excretion (UNaV) and urine volume (V) increased continuously to 56.2 +/- 2.7 (SE) mumol.min-1.kg body wt-1 and 482 +/- 23 microliters.min-1.kg body wt-1, respectively. UNaV and V increased less during PEEP in CMV 20 and CMV 20-ACEI. However, significantly more sodium and water were retained in CMV 20 than in CMV 20-ACEI (2.3 +/- 0.3 vs. 1.0 +/- 0.3 mmol/kg body wt, and 20 +/- 3 vs. 11 +/- 2 ml/kg body wt) because of a decrease of glomerular filtration rate and fractional UNaV in CMV 20. Heart rate did not change in control, CMV 20, or CMV 20-ACEI. Mean arterial pressure increased during control by 13 mmHg, did not change during CMV 20, and was decreased by 7 mmHg in CMV 20-ACEI.(ABSTRACT TRUNCATED AT 250 WORDS)

Rhythmicity of urinary sodium excretion, mean arterial blood pressure, and heart rate in conscious dogs.

The existence of urinary excretion rhythms in dogs, which is a matter of controversy, was investigated under strictly controlled intake and environmental conditions. In seven conscious dogs, 14.5 mmol Na, 3.55 mmol K, and 91 ml H2O.kg body wt-1.24 h-1 were either administered with food at 8:30 A.M. or were continuously infused at 2 consecutive days. During these 3 days, automatized 20-min urine collections, mean arterial blood pressure (MABP), and heart rate (HR) recordings were performed without disturbing the dogs. Fundamental and partial periodicities, the noise component of urinary sodium excretion (UNaV), MABP, and HR were analyzed using a method derived from Fourier and Cosinor analysis. Oral intake (OI) leads to powerful 24-h periodicities in all dogs and seems to synchronize UNaV. UNaV on OI peaked between 1 and 3 P.M. Under the infusion regimen, signs of nonstationary rhythms and desynchronization predominated. UNaV under the infusion regimen could be separated into two components: a rather constant component continuously excreted and superimposed to this an oscillating component. No direct coupling between UNaV and MABP periodicities could be demonstrated. On OI, an increase in HR seems to advance the peak UNaV in the postprandial period. HR and MABP signals were both superimposed with noise. We conclude that UNaV rhythms are present in dogs. They are considerably more pronounced on OI.

Prevention of catheter-related infections by a new, catheter-restricted antibiotic filling technique.

Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters. In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days. Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with alpha-chymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml). Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed. Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed. We conclude that filling only the catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections.

Effect of high sodium and high water intake on 24 h-potassium balance in dogs.

The influence of different amounts of oral sodium intake combined with high oral water intake on potassium excretion and plasma potassium concentration (PK) was evaluated. Female beagle dogs (11-16 kg) were divided into 2 groups: 1. Normal Sodium and high Water Intake (NSWI): 2.5 mmol Na, 3.55 mmol K, 91 ml H2O, and 277 kJ per kg body mass and 24 h (31 24 h-balance studies with 11 dogs). 2. High Sodium and high Water Intake (HSWI): Same diet as NSWI but 14.5 mmol Na x kg body mass-1 x 24 h-1 (55 24 h-balance studies with 21 dogs). The 24 h-balance studies were performed after different periods of time after onset of the respective diet (dogs in metabolic cages). Plasma sodium concentration (PNa) on NSWI was 148.4 +/- 2.6 mmol x 1(-1), whereas it was lower on HSWI (145.9 +/- 2.4 mmol x 1(-1). The lower plasma aldosterone concentration (PAC) on HSWI (24 +/- 8 pg x ml-1) compared to NSWI (67 +/- 38 pg x ml-1) may account for the lower PNa on HSWI. 24 h-sodium excretion was 93.6 +/- 6.5% of intake (%i) on HSWI and 91.5 +/- 20.7% i on NSWI. 24 h-water excretion was not different between both groups (81 +/- 7% i). PK was 3.93 +/- 0.25 mmol x 1(-1) on NSWI regardless of the time the dogs were on NSWI.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-assisted long-term measurements of urinary output and other biological data.

A computerized system is described, combining automatic collection of urine in short intervals (minutes) over long periods (days) and recordings of body temperature, MABP, and heart rate in chronically instrumented conscious dogs. During the studies the dogs are housed in metabolic cages. Indwelling catheters and electrical wires are connected to a specially designed swivel and directed out of the cage to the next room. Infusions, blood sampling, and monitoring can be performed from this room without disturbance to the dogs. Three examples of recordings are given. In one of these examples the sodium excretion patterns on 5 consecutive days under continuous saline infusion in one dog is evaluated. Urine was collected every 20 min. Sodium excretion showed cyclic variations. Fourier analysis exhibited 18-h periods and 4- to 8-h periods. The described system renders, e.g., coherent time series analysis possible for a variety of simultaneously recorded physiological variables and may thus acquire considerable importance for integrative physiology.

Acute effects of angiotensin II on renal haemodynamics and excretion in conscious dogs.

The effects of a 60-min intravenous infusion of angiotensin II (A II; 4 or 20 ng A II/min/kg body weight) on renal blood flow (RBF; electromagnetic flow transducer, control value 19-25 ml/min/kg), glomerular filtration rate (GFR; control value 4.2-5.0 ml/min/kg), mean arterial blood pressure, sodium excretion, water excretion, and plasma A II and plasma aldosterone concentrations were examined in 6 chronically instrumented female conscious beagle dogs kept on three different dietary sodium intakes (SI): SI 0.5 or SI 2.5 mmol Na/kg/day or SI 4.5 mmol Na/kg/day plus an oral saline load prior to the experiment SI 4.5(+) dogs. Four nanograms A II decreased RBF and GFR in SI 4.5(+) dogs without changing the filtration fraction (FF%); in SI 0.5 dogs the RBF decreased, and the FF% increased. Twenty nanograms A II decreased RBF and increased FF% in all dietary protocols, less in SI 4.5(+) dogs. The mean arterial blood pressure increased in all dietary protocols by 10-15 mm Hg (4 ng A II) and 32-37 mm Hg (20 ng A II). Sodium and water excretions decreased by 32 and 46%, respectively, in SI 4.5(+) dogs at both doses of A II. The plasma aldosterone concentration increased in all but one protocol: 4 ng A II, SI 4.5(+) dogs. It is concluded that when A II plasma concentrations are most likely borderline to pathophysiological conditions (up to an average of 370 pg/ml), the GFR is less decreased than the RBF. This phenomenon also can be observed at lower plasma A II concentrations (average 200 pg/ml), when the renin-angiotensin system had been previously moderately activated.