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Biomedical subjects

J L Andersen

Publications and source records attributed to J L Andersen.

At least 37 records · Page 2Linked to original sources

Neural inhibition during maximal eccentric and concentric quadriceps contraction: effects of resistance training.

Despite full voluntary effort, neuromuscular activation of the quadriceps femoris muscle appears inhibited during slow concentric and eccentric contractions. Our aim was to compare neuromuscular activation during maximal voluntary concentric and eccentric quadriceps contractions, hypothesizing that inhibition of neuromuscular activation diminishes with resistance training. In 15 men, pretraining electromyographic activity of the quadriceps muscles [vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF)] was 17-36% lower during slow and fast (30 and 240 degrees/s) eccentric and slow concentric contractions compared with fast concentric contractions. After 14 wk of heavy resistance training, neuromuscular inhibition was reduced for VL and VM and was completely removed for RF. Concurrently, electromyographic activity increased 21-52, 22-29, and 16-32% for VL, VM, and RF, respectively. In addition, median power frequency decreased for VL and RF. Eccentric quadriceps strength increased 15-17%, whereas slow and fast concentric strength increased 15 and 8%, respectively. Pre- and posttraining median power frequency did not differ between eccentric and concentric contractions. In conclusion, quadriceps motoneuron activation was lower during maximal voluntary eccentric and slow concentric contractions compared with during fast concentric contraction in untrained subjects, and, after heavy resistance training, this inhibition in neuromuscular activation was reduced.

Adult↗

Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of exercise training.

The fiber type-specific expression of skeletal muscle GLUT4 and the effect of 2 weeks of low-intensity training were investigated in 8 young untrained male subjects. Single muscle fibers were dissected from a vastus lateralis biopsy sample. Based on myosin heavy chain (MHC) expression, fibers were pooled into 3 groups (MHC I, MHC IIA, and MHC IIX), and the GLUT4 content of 15-40 pooled fibers was determined using SDS-PAGE and immunological detection. The GLUT4 content in pooled muscle fibers expressing MHC I was approximately 20% higher (P < 0.05) than that in muscle fibers expressing MHC IIA or MHC IIX. No difference in GLUT4 could be detected between fibers expressing MHC IIA or MHC IIX. Two weeks of exercise training increased (P < 0.05) the peak power output of the knee extensors by 13%, the maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase by 21 and 18%, respectively, and the GLUT4 protein content by 26% in a muscle homogenate. Furthermore, a 23% increase (P < 0.05) in GLUT4 was seen in fibers expressing the MHC I isoform after exercise training for 2 weeks. No change was seen in fibers expressing MHC IIA or MHC IIX. In conclusion, our data directly demonstrate that GLUT4 is expressed in a fiber type-specific manner in human skeletal muscle, although fiber type differences are relatively small. In addition, low-intensity exercise training recruiting primarily fibers expressing MHC I increased GLUT4 content in these fibers but not in fibers expressing MHC IIA or MHC IIX, indicating that GLUT4 protein content is related more to activity level of the fiber than to its fiber type, which is defined by expression of contractile protein.

Adult↗

Increase in the degree of coexpression of myosin heavy chain isoforms in skeletal muscle fibers of the very old.

Myosin heavy chain (MHC) isoform composition was determined in 2264 single skeletal muscle fibers from vastus lateralis muscle of a group (n = 12) of very old subjects (average age, 88 years). The number of fibers containing only MHC I, IIA, or IIX was 19.9%, 27.2%, and 0.3%, respectively. Surprisingly, 28.5% of the fibers displayed coexpression of both MHC I and IIA, a phenotype that is present in younger adults in very small percentages. Among these fibers coexpressing MHC I and IIA, the majority had a dominant expression of MHC I. Additionally, a small number of fibers coexpressing MHC I and IIX without any MHC IIA, and fibers co-expressing all three isoforms were observed. Altogether, 52.6% of all fibers examined in these very old subjects coexpressed two or three MHC isoforms. The present study provides evidence that advanced age leads to a significant elevation of skeletal muscle fibers displaying coexpression of two MHC isoforms and that a separation into slow and fast fibers in very old individuals may therefore be somewhat misleading. The clinical significance of the elevated number of fibers coexpressing MHC I and IIA is uncertain.

Aged↗

High expression of MHC I in the tibialis anterior muscle of a paraplegic patient.

A long-term paraplegic man presented exclusively (>99%) myosin heavy chain I (MHC I) in the tibialis anterior muscle (TA). This was coupled to a slow speed of contraction, a high resistance to fatigue, and a rapid resynthesis of phosphocreatine after an electrically evoked fatiguing contraction when compared with the TA muscles of 9 other paraplegic individuals. In contrast, the MHC composition of his vastus lateralis, gastrocnemius, and soleus muscles was that expected of a muscle from a spinal cord injured individual. This information may be of clinical importance in terms of the expected morphological and functional adaptations of skeletal muscle to different types of electrical stimulation therapy.

Electromyography↗

Bed rest increases the amount of mismatched fibers in human skeletal muscle.

The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expression on both mRNA and protein level in human skeletal muscle fibers were studied. Muscle biopsies from vastus lateralis muscle were obtained from seven healthy young male subjects before and after the bed-rest period. Combined in situ hybridization, immunocytochemistry, and ATPase histochemistry analysis of serial sections of the muscle biopsies demonstrated that fibers showing a mismatch between MHC isoforms at the mRNA and protein level increased significantly after the bed-rest period, suggesting an increase in the amount of muscle fibers in a transitional state. Accordingly, fibers showing a match in expression of MHC-1 and of MHC-2A at the mRNA and protein level decreased, whereas fibers showing a match between MHC-2X mRNA and protein increased after bed rest. Overall, there was an increase in fibers in a transitional state from phenotypic type 1 --> 2A and 2A --> 2X. Furthermore, a number of fibers with unusual MHC mRNA and isoprotein combinations were observed after bed rest (e.g., type 1 fibers with only mRNA for 2X and type 1 fibers negative for mRNA for MHC-beta/slow, 2A, and 2X). In contrast, no changes were revealed after an examination at the protein level alone. These data suggest that the reduced load-bearing activity imposed on the skeletal muscles through bed rest will alter MHC gene expression, resulting in combinations of mRNA and MHC isoforms normally not (or only rarely) observed in muscles subjected to load-bearing activity. On the other hand, the present data also show that 37 days of bed rest are not a sufficient stimulus to induce a similar change at the protein level, as was observed at the gene level.

Adenosine Triphosphatases↗

Correlation between contractile strength and myosin heavy chain isoform composition in human skeletal muscle.

PURPOSE: The purpose of this study was to investigate the relationship between myosin heavy chain (MHC) composition and maximal contraction strength of the human quadriceps femoris muscle. METHODS: Muscle biopsies were obtained from m. vastus lateralis in your highly physical active males (N = 7). The MHC composition of muscle homogenates was determined by electrophoresis techniques (SDS-PAGE). Isokinetic peak torque and constant-angle torque (50 degrees knee flexion) were obtained during slow (30 degrees.s-1), medium (120 degrees.s-1), and fast (240 degrees.s-1) maximal concentric and eccentric quadriceps contractions and expressed relative to muscle volume. RESULTS: The percentage of MHC II in the quadriceps muscle was positively correlated (rs = 0.61-0.93; P < 0.05-0.01) to maximal concentric quadriceps strength obtained at medium to high knee angular velocity. In contrast, no consistent pattern of correlation was observed for maximal eccentric quadriceps strength. CONCLUSIONS: The relationship observed between muscular MHC composition and maximal contractile strength is suggested to appear as a consequence of MHC -related differences in contractile force-velocity characteristics and/or contractile Rate of Force Development (RFD).

Adult↗

Visualisation of capillaries in human skeletal muscle.

A double staining method combining Ulex europaeus agglutinin I lectin (UEA-I) and collagen type IV staining was used to determine the capillary density and the number of capillaries relative to different fibre types in human skeletal muscles. The result of this combined staining was compared with that of other staining methods including amylase-periodic acid Schiff (PAS), UEA-I, anti-collagen type IV and anti-von Willebrand factor. Muscle biopsy specimens, 12 from M. vastus lateralis and 6 from M. soleus, were obtained from 18 healthy young men. Compared with amylase-PAS staining, double staining showed a larger number of capillaries surrounding type I (+9.6%), type IIA (+8.6%) and type IIB (+11.6%) fibres in the M. vastus lateralis specimens (P < 0.001 for all differences). The capillary to fibre ratio (cap fibre-1) and the capillary density (cap.mm-2) were 8.3% (P < 0.002) and 7.9% (P < 0.001) larger, respectively. In the M. soleus specimens, cap.fibre-1 and cap.mm-2 were 7.4 and 9.9% larger, respectively, by double staining compared with PAS staining. Further comparisons showed that the cap.fibre-1 and cap.mm-2 obtained with double staining were similar to the values determined by the UEA-I staining, but greater than that measured by the collagen type IV method. The double staining gave a more marked stain of capillaries and revealed muscle fibre borders clearly, which is an advantage in studies that require comparisons between serial sections using computerised image analyses. It is concluded that the double staining method is superior to either the UEA-I, collagen type IV or the traditional amylase-PAS staining methods in analysing capillary density of normal human skeletal muscle.

Adolescent↗

Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals.

Spinal cord injured (SCI) individuals most often contract their injury at a young age and are deemed to a life of more or less physical inactivity. In addition to the primary implications of the SCI, severe SCI individuals are stigmatized by conditions related to their physically inactive lifestyle. It is unknown if these inactivity related conditions are potentially reversible and the aim of the present study was, therefore, to examine the effect of exercise on SCI individuals. Ten such individuals (six with tetraplegia and four with paraplegia; age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year using an electrically induced computerized feedback controlled cycle ergometer. They trained for up to three times a week (mean 2.3 times), 30 min on each occasion. The gluteal, hamstring and quadriceps muscles were stimulated via electrodes placed on the skin over their motor points. During the first training bouts, a substantial variation in performance was seen between the subjects. A majority of them were capable of performing 30 min of exercise in the first bout; however, two individuals were only able to perform a few minutes of exercise. After training for 1 year all of the subjects were able to perform 30 min of continuous training and the work output had increased from 4 +/- 1 (mean +/- SE) to 17 +/- 2 Kilo Joules per training bout (P < 0.05). The maximal oxygen uptake during electrically induced exercise increased from 1.20 +/- 0.08 litres per minute measured after a few weeks habituation to the exercise to 1.43 +/- 0.09 litres per minute after training for 1 year (P < 0.05). Magnetic resonance cross sectional images of the thigh were performed to estimate muscle mass and an increase of 12% (mean, P < 0.05) was seen in response to 1 year of training. In biopsies taken before exercise various degrees of atrophy were observed in the individual muscle fibres, a phenomenon that was partially normalized in all subjects after training. The fibre type distribution in skeletal muscles is known to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic fibres) within the first 2 years after the spinal cord injury. The muscle in the present investigation contained of 63% myosin heavy chain (MHC) isoform IIB, 33% MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I (slow twitch) before training. A shift towards more fatigue resistant contractile proteins was found after 1 year of training. The percentage of MHC isoform IIA increased to 61% of all contractile protein and a corresponding decrease to 32% was seen in the fast fatiguable MHC isoform IIB, whereas MHC isoform I only comprised 7% of the total amount of MHC. This shift was accompanied by a doubling of the enzymatic activity of citrate synthase, as an indicator of mitochondrial oxidative capacity. It is concluded that inactivity-associated changes in exercise performance capacity and skeletal muscle occurring in SCI individuals after injury are reversible, even up to over 20 years after the injury. It follows that electrically induced exercise training of the paralysed limbs is an effective rehabilitation tool that should be offered to SCI individuals in the future.

Adaptation, Physiological↗

Mismatch between myosin heavy chain mRNA and protein distribution in human skeletal muscle fibers.

The distribution of myosin heavy chain (MHC) isoforms was analyzed at the protein and mRNA levels in human skeletal muscle biopsies from young normal adult subjects. Using ATPase histochemical reactions, antibodies to fast- and slow-type MHCs, and in situ hybridization with probes specific for MHC-beta/slow, MHC-2A, and MHC-2X, we confirmed our previous results showing that most fibers contain either a single mRNA and isoprotein or a mixed 1/2A or 2A/2X phenotype with coexistence of two mRNAs and isoproteins. However, we also found a minor proportion of fibers showing a mismatch in the relative proportion of mRNA and protein, e.g., fibers containing MHC-2A mRNA but not the corresponding protein or fibers containing MHC-2A protein but not the corresponding transcript. These fibers were more frequent in biopsies obtained after a training or detraining period than before the training period. We propose that these fibers represent transitional fibers and that the relative content of each mRNA and isoprotein gives a clue as to the direction of change in MHC gene expression.

Adult↗

Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM.

Insulin resistance is a common feature in first-degree relatives of NIDDM patients. To explore the mechanism(s) behind this condition in more detail, a percutaneous muscle biopsy (vastus lateralis) was performed in 25 first-degree relatives of NIDDM patients and 21 control subjects to examine muscle fiber composition and capillary density. Insulin-stimulated glucose disposal (Rd) was determined employing a hyperinsulinemic-(insulin infusion rate 0.6 mU x kg[-1] x min[-1]) euglycemic clamp. Rd (5.76 +/- 0.35 vs. 8.06 +/- 0.36 mg x kg lean body weight [LBW]-1 x min[-], P < 0.001) and estimated VO2max (49.3 +/- 2.8 vs. 57.2 +/- 3.5 mg x kg LBW[-1] x min[-1], 0.05 < P < 0.10) were decreased in the relatives. The number of type IIb fibers (29.5 +/- 2.5 vs. 21.0 +/- 2.8%, P < 0.05) was increased in the relatives, whereas no significant differences were found in other fiber types or capillary density between the groups. Correlations were observed between number of type I fibers (positive), number of type IIb fibers (negative), and capillary density (positive) versus Rd as well as estimated VO2max (P < 0.05). In a multiple linear regression analysis with Rd as a dependent variable, estimated VO2max, family history of NIDDM, and number of type IIb fibers (P < 0.001, r2 = 0.64) significantly determined the level of Rd, whereas capillary density did not. In conclusion, insulin-resistant first-degree relatives of NIDDM patients are characterized by an increased number of type IIb muscle fibers. Whether this finding reflects a reduced physical activity level and fitness in the relatives or is of primary genetic origin remains to be determined.

Adult↗

Myosin heavy chain isoform transformation in single fibres from m. vastus lateralis in spinal cord injured individuals: effects of long-term functional electrical stimulation (FES).

The myosin heavy chain (MHC) composition of single fibres from m. vastus lateralis of five spinal- cord-injured (SCI) individuals was analysed by Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) before, and after 6 and 12 months of functional electrical stimulation (FES)-training, administrated for 30 min three times per week. Prior to FES training 37.2% of the fibres contained only MHC IIB, 21.2% only MHC IIA, and 40.7% co-expressed MHC IIA and MHC IIB. After 6 months of FES-training the number of fibres containing only MHC IIB was reduced to 2.6% (P < 0.05), the number of fibres containing only MHC IIA was increased to 44.3% (P < 0.05), and the number of fibres co-expressing MHC IIA and MHC IIB was 50.9% (ns). After 12 months almost all fibres (91.2%, P < 0.05) contained only MHC IIA. The number of fibres containing only MHC IIB was 2.3% and the fibres co-expressing MHC IIA and IIB had decreased to 4.6% (P < 0.05). The amount of fibres containing only MHC I never exceeded 0.5%. Likewise, the number of fibres co-expressing MHC I and MHC IIA was below 2% throughout the study period. In total, the MHC composition of 1596 single fibres was determined. This study shows that FES-training of paralysed human skeletal muscle administrated over a prolonged period of time, can lead to a marked switch in MHC expression from about equal amounts of MHC IIA and MHC IIB to an almost total dominance of MHC IIA.

Adult↗

Sun exposure and sunscreen use among sunbathers in Denmark.

Eight hundred and eight sunbathing Danes were interviewed in order to register the duration of sun exposure and sunscreen use. The mean sun exposure time, 203 min, was found to be independent of sex, age and use of sunscreen. Overall, sunscreens were used by 65%, 73% of the females and 52% of the males. The median sun protection factor used by subjects older than 10 years was 5; in the case of children 10 years or younger, it was 12. Eight per cent of the interviewed subjects used more than one factor. Fifty-seven per cent of the sunscreen users applied the sunscreen prior to arriving at the beach. The sun exposure time was not significantly different in the group of subjects using sunscreens, compared to the group of subjects not using sunscreens. This study indicates that sunscreen users may not increase their exposure to the sun.

Adult↗

Delayed initiation of breast-feeding the preterm infant.

It is well documented that mother's milk is the best source of nutrition for the preterm infant. However, mothers of preterm infants face obstacles during the early stages of the breast-feeding experience. This study examined the experiences of 13 mothers whose preterm infants initiated suckling at the breast on day 14 or later after birth. Eight weeks after delivery, six infants were exclusively receiving mother's milk, four were receiving mother's milk and formula, and three infants had been weaned entirely from mother's milk. Some of the problems encountered by these mothers may have been averted with input from health professionals with special knowledge in breast-feeding the preterm infant. A clinical pathway for breast-feeding preterm infants is presented.

Adult↗

Effect of loading right atrial and ventricular receptors on stimulated AVP, ACTH, and renin secretion in awake dogs.

The goal of this study was to test the hypothesis that increasing or decreasing the load on baroreceptors in the right heart influenced the secretion of arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and renin during a state of sustained arterial hypotension. The hypothesis was tested in chronically instrumented conscious dogs prepared with inflatable cuffs around the pulmonary artery (PA) and the thoracic inferior vena cava (IVC). In one protocol (n = 5), mean arterial pressure was reduced 10 or 20% below control by constriction of the PA, a maneuver that caused a fall in left atrial pressure (LAP) and an increase in right atrial pressure (RAP). Plasma AVP, ACTH, atrial natriuretic peptide (ANP), and plasma renin activity (PRA) all increased (P < 0.05) in response to constriction of the PA. Reducing RAP to control by constriction of the IVC during maintained constriction of the PA had no effect on MAP, LAP, plasma AVP, ACTH, or PRA, but plasma ANP fell significantly. In a separate protocol (n = 4), constriction of the IVC was used to reduce MAP 10 or 20% below control, and this led to significant decreases in both LAP and RAP and increases in plasma AVP, ACTH, and PRA. RAP was then increased above control by constriction of the PA without altering either MAP or LAP. Raising RAP from a level that was 6.3 +/- 1.3 mmHg below control to 3.5 +/- 1.0 mmHg above control had no effect on plasma AVP, ACTH, or PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Myosin heavy chain isoforms in single fibres from m. vastus lateralis of soccer players: effects of strength-training.

The myosin heavy chain (MHC) composition of single fibres (n = 2171) was analysed with an electrophoretic technique in biopsy material from m. vastus lateralis of two groups of soccer players before and after a 3-month period of either strength- (n = 8) or non-training (control) (n = 6). Traditional myofibrillar ATPase histochemistry demonstrated a decrease in type IIA fibres with strength-training (35.4 +/- 2.1 vs. 26.7 +/- 2.4% (P < 0.05)). This was not observed in the non-training group (25.7 +/- 4.6 vs. 23.8 +/- 1.7%). One-dimensional electrophoresis on muscle homogenates showed no significant change in the amount of MHC isoforms in either of the two groups. The MHC isoform IIB was undetectable in all but three samples. No changes in the proportions of fibres containing any of the MHC isoforms were observed. Fibres containing only MHC isoform IIB were found in very small numbers (only 11 out of 2171). Before the experimental period, between 6 and 10% histochemical type IIB fibres were found in both groups. This was identical with the proportion of fibres showing co-existence of MHC isoforms IIA and IIB, but in contrast to the very few fibres containing only MHC isoform IIB. This suggests that nearly all histochemical type IIB fibres of the soccer players display co-existence of both MHC isoform IIA and IIB. No major change in the muscle fibre area of the two groups was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myosin heavy chain isoforms in single fibres from m. vastus lateralis of sprinters: influence of training.

The myosin heavy chain (MHC) composition of single fibres from m. vastus lateralis of a group of male sprint athletes (n = 6) was analysed, before and after a three months period of intensive strength- and interval-training, using a sensitive gel electrophoretic technique. Significant improvements were observed after training in almost all of a series of performance tests. After training the sprinters revealed a decrease in fibres containing only MHC isoform I (52.0 +/- 3.0% vs. 41.2 +/- 4.7% (mean +/- SE) (P < 0.05)) and an increase in the amount of fibres containing only MHC isoform IIA (34.7 +/- 6.1% vs. 52.3 +/- 3.6% (P < 0.05)). Fibres showing co-existence of MHC isoforms IIA and IIB decreased with training (12.9 +/- 5.0% vs. 5.1 +/- 3.1% (P < 0.05)). Only one out of 1000 fibres analysed contained only MHC isoform IIB. In contrast, a higher amount of type IIB fibres (18.8 +/- 3.6% vs. 10.5 +/- 3.9%, (P < 0.05)) was observed with myofibrillar ATPase histochemistry. The majority of histochemically determined type IIB fibres of sprinters seems therefore to contain both MHC isoforms IIA and IIB. Sprint-training appears to induce an increased expression of MHC isoform IIA in skeletal muscles. This seems related to a bi-directional transformation from both MHC isoforms I and IIB towards MHC isoform IIA.

Adult↗

Left heart and arterial baroreceptors interact in control of plasma vasopressin, renin, and cortisol in awake dogs.

Arterial hypotension induced by constriction of the ascending aorta (AA) causes increases in left atrial pressure (LAP) and plasma atrial natriuretic peptide (ANP), but no change in plasma arginine vasopressin (AVP), plasma renin activity (PRA), or cortisol. In the present study, we tested the hypothesis that the rise in left heart pressure during constriction of the AA suppressed the stimulation of AVP, renin, and cortisol secretion in response to arterial hypotension. Dogs were prepared with inflatable cuffs around the AA, the pulmonary artery (PA), and the thoracic inferior vena cava (IVC) and with catheters in the left and right atria and abdominal aorta. In one series of experiments, the AA was constricted to lower mean arterial pressure (MAP) 10 or 20% below control for 15 min. Then, either the PA or the IVC was constricted to bring LAP back to control levels but without altering the degree of arterial hypotension. Constriction of the AA alone led to significant increases in LAP and plasma ANP but no change in plasma AVP, cortisol, or PRA. Reducing LAP to control levels by constriction of either the PA or IVC led to significant and similar increases in plasma AVP, cortisol, and PRA. Plasma ANP fell significantly 10 min after LAP was normalized by constriction of the IVC but not when LAP was normalized by constriction of the PA, because PA constriction caused a significant rise in right atrial pressure that stimulated ANP secretion. The increases in plasma AVP and PRA after normalizing LAP by constriction of the PA were compared with the increases obtained during identical falls in MAP induced by constriction of the IVC alone, a maneuver that lowers LAP below control. The increases in plasma AVP in the two conditions were identical, indicating that the stimulation of left heart baroreceptors alone can account for the suppression of AVP secretion in response to unloading arterial baroreceptors. In contrast, there was a greater rise in PRA during hypotension caused by constriction of the IVC alone compared with the condition in which LAP was normalized but plasma ANP remained elevated. This suggests that increased left heart pressure inhibits renin secretion in response to arterial hypotension by reflex mechanisms and by increased plasma ANP concentration.

Animals↗

Antidiuretic effect of subnormal levels of arginine vasopressin in normal humans.

The renal responses to 120-min infusions of arginine vasopressin (AVP) were investigated in healthy volunteers undergoing water diuresis induced by an oral water load of 20 ml/kg body wt. AVP at 1 pg.min-1.kg-1 (approximately 10(-15) mol.min-1.kg-1) decreased urine flow (12.2 +/- 1.7 to 7.4 +/- 1.5 ml/min) and free water clearance (9.7 +/- 1.5 to 4.8 +/- 1.4 ml/min) and increased urine osmolality (Uosmol; 71 +/- 6 to 115 +/- 15 mosmol/kgH2O); 5 pg.min-1.kg-1 elicited pronounced antidiuresis (14.4 +/- 0.9 to 0.9 +/- 0.3 ml/min) with maximal Uosmol of 621 +/- 95 mosmol/kg. In response to 25 pg.min-1.kg-1, maximal Uosmol was 869 +/- 38 mosmol/kg. Responses developed gradually and stabilized within the 2nd h of infusion. AVP at 1 and 5 pg.min-1.kg-1 was without effect for at least 20 min. Only 25 pg.min-1.kg-1 caused a significant rise in plasma AVP (1.2 +/- 0.2-2.0 +/- 0.1 pg/ml), and with this dose sodium excretion decreased. The rates of K+ excretion, as well as plasma aldosterone and atrial natriuretic peptide concentrations, were unaffected by AVP. It is concluded that the human kidney is sensitive to changes in the rate of secretion of AVP of less than 1 pg.min-1.kg-1 and that the maximal change occurs after 1-2 h of constant infusion. It is estimated that the rate of infusion of AVP required to produce isosmolar urine during overhydration is approximately 3 pg.min-1.kg-1.

Adult↗