Healthy Human System Research Articles

Consequences of Acute Stress and Alcohol Exposure on the Endo-cannabinoid System in Healthy Humans

Consequences of Acute Stress and Alcohol Exposure on the Endo-cannabinoid System in Healthy Humans

The incretin system in healthy humans: The role of GIP and GLP-1

The incretin effect, the amplification of insulin secretion occurring when glucose is taken in orally as compared to infused intravenously, is one of the factors that help the body to tolerate carbohydrate/glucose ingestion. These include 1) amount and type of carbohydrates; 2) gastric emptying rate; 3) digestion and absorption of the carbohydrates; 4) secretion and effect of the incretin hormones; 5) disposition of absorbed nutrients/glucose. The incretin effect can also be viewed as the fraction of the ingested glucose load handled via gastrointestinal mechanisms (including the incretin effect); it is calculated by comparison of the amount of glucose required to copy, by intravenous infusion, the oral load. Typically, for 75 g of oral glucose, about 25 g are required. This means that the GastroIntestinal Glucose Disposal (GIGD) is 66%. Both the GIGD and the incretin effect depend on the amount of glucose ingested: for higher doses the GIGD may amount to 80%, which shows that this effect is a major contributor to glucose tolerance. The main mechanism behind it is stimulation of insulin secretion by a proportional secretion of the insulinotropic hormones GIP and GLP-1. Recently it has become possible to estimate their contributions in healthy humans using specific and potent receptor antagonists. Both hormones act to improve glucose tolerance (i.e. the antagonists impair tolerance) and their effects are additive. GIP seems to be quantitatively the most important, particularly regarding insulin secretion, whereas the action of GLP-1 is mainly displayed via inhibition of glucagon secretion.

Consumption of orange fermented beverage improves antioxidant status and reduces peroxidation lipid and inflammatory markers in healthy humans.

Alcoholic fermentation of fruits has generated novel products with high concentrations of bioactive compounds and moderate alcohol content. The aim of this study was to evaluate the potential effect on cardiovascular risk factors of the regular consumption by healthy humans of a beverage obtained by alcoholic fermentation and pasteurization of orange juice. Thirty healthy volunteers were enrolled in a randomized controlled study. The experimental group (n = 15) drank 500 mL orange beverage (OB) per day for 2 weeks (intervention phase), followed by a 3-week washout phase. Blood samples were collected at baseline (E-T0) and at the end of the intervention (E-T1) and washout (E-T2) phases. Controls (n = 15) did not consume OB during a 2-week period. OB intake significantly increased oxygen radical absorbance capacity (43.9%) and reduced uric acid (-8.9%), catalase (CAT) (-23.2%), thiobarbituric acid reactive substances (TBARS) (-30.2%) and C-reactive protein (-2.1%) (E-T1 vs. E-T0). These effects may represent longer-term benefits, given the decreased uric acid (-8.9%), CAT (-34.6%), TBARS (-48.4%) and oxidized low-density lipoprotein (-23.9%) values recorded after the washout phase (E-T2 vs. E-T0). The regular consumption of OB improved antioxidant status and decreased inflammation state, lipid peroxidation and uric acid levels. Thus OB may protect the cardiovascular system in healthy humans and be considered a novel functional beverage. © 2017 Society of Chemical Industry.

Resting state Rolandic mu rhythms are related to activity of sympathetic component of autonomic nervous system in healthy humans

We tested the hypothesis of a relationship between heart rate variability (HRV) and Rolandic mu rhythms in relaxed condition of resting state. Resting state eyes-closed electroencephalographic (EEG) and electrocardiographic (ECG) data were recorded (10–20 System) in 42 healthy adults. EEG rhythms of interest were high-frequency alpha (10.5–13Hz) and low-frequency beta (13–20Hz), which are supposed to form Rolandic mu rhythms. Rolandic and occipital (control) EEG sources were estimated by LORETA software. Results showed a statistically significant (p<0.05, corrected) negative correlation across all subjects between Rolandic cortical sources of low-frequency beta rhythms and the low-frequency band power (LF, 0.04–0.15Hz) of tachogram spectrum as an index of HRV. The lower the amplitude of Rolandic sources of low-frequency beta rhythms (as a putative sign of activity of somatomotor cortex), the higher the LF band power of tachogram spectrum (as a putative sign of sympathetic activity). This effect was specific as there was neither a similar correlation between these EEG rhythms and high-frequency band power of tachogram spectrum (as a putative sign of parasympathetic vagal activity) neither between occipital sources of low-frequency beta rhythms (as a putative sign of activity of visual cortex) and LF band power of tachogram spectrum. These results suggest that Rolandic low-frequency beta rhythms are related to sympathetic activity regulating heart rate, as a dynamic neurophysiologic oscillatory mechanism sub-serving the interaction between brain neural populations involved in somatomotor control and brain neural populations regulating ANS signals to heart for on-going homeostatic adaptations.

Positive or Negative Feedback of Optokinetic Signals: Degree of the Misrouted Optic Flow Determines System Dynamics of Human Ocular Motor Behavior

The optokinetic system in healthy humans is a negative-feedback system that stabilizes gaze: slow-phase eye movements (i.e., the output signal) minimize retinal slip (i.e., the error signal). A positive-feedback optokinetic system may exist due to the misrouting of optic fibers. Previous studies have shown that, in a zebrafish mutant with a high degree of the misrouting, the optokinetic response (OKR) is reversed. As a result, slow-phase eye movements amplify retinal slip, forming a positive-feedback optokinetic loop. The positive-feedback optokinetic system cannot stabilize gaze, thus leading to spontaneous eye oscillations (SEOs). Because the misrouting in human patients (e.g., with a condition of albinism or achiasmia) is partial, both positive- and negative-feedback loops co-exist. How this co-existence affects human ocular motor behavior remains unclear. We presented a visual environment consisting of two stimuli in different parts of the visual field to healthy subjects. One mimicked positive-feedback optokinetic signals and the other preserved negative-feedback optokinetic signals. By changing the ratio and position of the visual field of these visual stimuli, various optic nerve misrouting patterns were simulated. Eye-movement responses to stationary and moving stimuli were measured and compared with computer simulations. The SEOs were correlated with the magnitude of the virtual positive-feedback optokinetic effect. We found a correlation among the simulated misrouting, the corresponding OKR, and the SEOs in humans. The proportion of the simulated misrouting needed to be greater than 50% to reverse the OKR and at least greater than or equal to 70% to evoke SEOs. Once the SEOs were evoked, the magnitude positively correlated to the strength of the positive-feedback OKR. This study provides a mechanism of how the misrouting of optic fibers in humans could lead to SEOs, offering a possible explanation for a subtype of infantile nystagmus syndrome (INS).

25-Hydroxyvitamin D status, arterial stiffness and the renin–angiotensin system in healthy humans

Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p = 0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p = 0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates (p = 0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism.

Kinetics of the utilization of dietary arginine for nitric oxide and urea synthesis: insight into the arginine–nitric oxide metabolic system in humans

The systemic availability of oral/dietary arginine and its utilization for nitric oxide (NO) synthesis remains unknown and may be related to a competitive hydrolysis of arginine into urea in the splanchnic area and systemic circulation. We investigated the kinetics and dose-dependency of dietary arginine utilization for NO compared with urea synthesis and studied the characteristics of the arginine-NO metabolic system in healthy humans. We traced the metabolic fate and analyzed the utilization dynamics of dietary arginine after its ingestion at 2 nutritional amounts in healthy humans (n = 9) in a crossover design by using [(15)N-(15)N-(guanido)]-arginine, isotope ratio mass spectrometry techniques, and data analysis with a compartmental modeling approach. Whatever the amount of dietary arginine, 60 ± 3% (±SEM) was converted to urea, with kinetics indicative of a first-pass splanchnic phenomenon. Despite this dramatic extraction, intact dietary arginine made a major contribution to the postprandial increase in plasma arginine. However, the model identified that the plasma compartment was a very minor (~2%) precursor for the conversion of dietary arginine into NO, which, in any case, was small (<0.1% of the dose). The whole-body and plasma kinetics of arginine metabolism were consistent with the suggested competitive metabolism by the arginase and NO synthase pathways. The conversion of oral/dietary arginine into NO is not limited by the systemic availability of arginine but by a tight metabolic compartmentation at the systemic level. We propose an organization of the arginine metabolic system that explains the daily maintenance of NO homeostasis in healthy humans.

Motor consequences of experimentally induced limb pain: A systematic review

Compelling evidence exists that pain may affect the motor system, but it is unclear if different sources of peripheral limb pain exert selective effects on motor control. This systematic review evaluates the effects of experimental (sub)cutaneous pain, joint pain, muscle pain and tendon pain on the motor system in healthy humans. The results show that pain affects many components of motor processing at various levels of the nervous system, but that the effects of pain are largely irrespective of its source. Pain is associated with inhibition of muscle activity in the (painful) agonist and its non-painful antagonists and synergists, especially at higher intensities of muscle contraction. Despite the influence of pain on muscle activation, only subtle alterations were found in movement kinetics and kinematics. The performance of various motor tasks mostly remained unimpaired, presumably as a result of a redistribution of muscle activity, both within the (painful) agonist and among muscles involved in the task. At the most basic level of motor control, cutaneous pain caused amplification of the nociceptive withdrawal reflex, whereas insufficient evidence was found for systematic modulation of other spinal reflexes. At higher levels of motor control, pain was associated with decreased corticospinal excitability. Collectively, the findings show that short-lasting experimentally induced limb pain may induce immediate changes at all levels of motor control, irrespective of the source of pain. These changes facilitate protective and compensatory motor behaviour, and are discussed with regard to pertinent models on the effects of pain on motor control.

Pathological Changes in Neurons of the Mesocorticolimbic Dopaminergic System in Healthy Humans and Rats

The aim of the present work was to identify normal levels of pathologically altered neurons and the intensity of neuron-glial interactions in interconnected parts of the mesoaccumbocingulate dopaminergic system (MDS) of the brain in adult intact female Wistar rats (n = 6) and healthy humans aged 24‐45 years (n = 5). The proportions of unaltered, hypochromic, pyknomorphic, and ghost neurons were identified in the anteromedial segment of the paranigral nucleus of the ventral tegmental area (VTA) and the compact zone of the substantia nigra, in the central medial part of the nucleus accumbens (NA) close to the anterior commissure of the brain, and the central part of layer III of the pregenual part of field 24b (Cg3 in rats). Controls consisted of brain formations which are not part of the MDS, i.e., layers III and V of field 1. Our data provide evidence of significant changes in MDS neurons in healthy people as compared with the level of changes in intact rats. The number of pathologically altered MDS neurons in humans decreased with increases in the distance from the catecholaminergic nuclei of the reticular formation, as did the number of fibers in the medial forebrain bundle, reaching a minimum in the non-dopaminoceptive and low-noradrenalinoceptive layer V of field 1. In the VTA, more than 25% of neurons were ghost cells. More than 30% of NA neurons were hypochromic and ghosted. About 25% of neurons in field 24b were ghost cells, hypochromic, and pyknomorphic. The intensities of neuron-glial interactions in the dopaminergic nuclei in humans and intact rats were significantly greater than in the projection areas of the MDS and the non-MDS layers of field 1. Local changes in human MDS neurons and the high intensity of neuron-glial interactions in the dopaminergic nuclei reflect blurring of the boundaries between normal conditions and pathology and the lower durability of this system as compared with cortical fields distant from the origin of catecholaminergic fibers.

Antiphase signalling in the neuroendocrine-immune system in healthy humans

Background Any quantity varying in the spatial-temporal dimension may be considered as a signal. Human lymphocyte cell surface molecules and subsets present circadian variation and this variation may represent a kind of signalling in the neuroendocrine-immune system. We have analyzed the dynamics of variation of specific lymphocyte subsets in healthy humans. Subjects and methods In our study, lymphocyte subpopulation analyses were performed and cortisol, melatonin, GH and TSH serum levels were measured on blood samples collected every 4 h for 24 hours from eleven healthy men, ages 35–53 years (mean = 44 ± 6 SD). Results A clear circadian rhythm was validated for CD8 and cortisol with acrophase during the day and for CD3, CD4, melatonin, GH and TSH with acrophase at night. Cross-correlation showed that CD3 correlated positively with CD4 ( ρ = 0.67, P < 0.05) and negatively with CD8 ( ρ = −0.41, P < 0.05), CD4 correlated positively with melatonin ( ρ = 0.90, P < 0.05), GH ( ρ = 0.92, P < 0.05) and TSH ( ρ = 0.71, P < 0.05), negatively with CD8 ( ρ = −0.90, P < 0.05) and cortisol ( ρ = −0.18, P < 0.05), CD8 correlated positively with cortisol ( ρ = 0.38, P < 0.05). Discussion The different profiles of nyctohemeral changes of lymphocyte cell surface molecules and specific lymphocyte subsets realize different relationships with the neuroendocrine hormones and might represent a way of signal transmission among the multiple components of the neuroendocrine-immune system.

Gender and the Renal Nitric Oxide Synthase System in Healthy Humans

It is widely known that men with kidney disease progress to ESRD at a much greater rate than do women. The mechanism for these gender differences is not clear, but reduced availability of nitric oxide is thought to contribute to the age-related decline in renal plasma flow observed in both healthy men and women. Animal models suggest that the renal vasculature of men may be significantly more dependent on nitric oxide than that of women. Renal plasma flow response to the nonspecific nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L-NAME) was measured by para-aminohippurate clearance technique in 21 healthy, normotensive (8 male, 13 female) individuals in balance on a high-salt diet. There were striking differences between the genders in the renal hemodynamic response to L-NAME according to age, a difference that remained even after adjustment for other significant covariates. In men, the fall in renal plasma flow induced by L-NAME increased remarkably with increasing age. In women, there was no influence of age on the renovascular response to L-NAME. Neither age nor gender predicted the mean arterial pressure response to L-NAME. The renal vasculature of men becomes more dependent on nitric oxide with age compared with that of women, suggesting that any renal disease that interferes with nitric oxide production may, over time, cause existent kidney damage to progress more quickly in men relative to women.

The natriuretic peptide system: kidney and cardiovascular effects

The natriuretic peptide (NP) system is primarily an endocrine system that maintains fluid and pressure homeostasis by modulating cardiac and renal function. The physiologic functions of the NP system in healthy humans and in patients with cardiovascular disease are not fully understood. NP levels are elevated in patients with heart failure (HF) and other cardiac diseases; measurement of NPs may be used in the clinical setting to aid diagnosis and prognosis. In addition, synthetic NPs such as nesiritide are available for use in management of patients with acutely decompensated congestive HF. Not only do NPs modulate volume and pressure homeostasis, but they also exert important anti-proliferative, anti-fibrotic effects in the heart. Thus, NPs may prove useful for prevention of remodeling after myocardial infarction and in advanced HF. BNP is emerging as an important biomarker in patients with HF and other cardiovascular diseases, such as pulmonary hypertension and atherosclerotic vascular disease. Elevated NP levels may serve as an early warning system to help to identify patients at high risk for cardiac events. Recombinant human ANP (carperitide) and BNP (nesiritide) are useful for management of acutely decompensated HF; these drugs are also being investigated for myocardial and renal protection in the setting of cardiac surgery and for prevention of cardiac remodeling. The clinical application of NPs is expanding rapidly. Recent basic science and clinical research findings continue to improve our understanding of the NP system and guide use of ANP and BNP as biomarkers and as therapeutic agents.

Effects of specific COX-2-inhibition on renin release and renal and systemic prostanoid synthesis in healthy volunteers

The renin-angiotensin system plays a critical role in cardiovascular function, but little is known about the effects of specific cyclooxygenase 2 (COX-2) inhibition on this system in healthy humans under physiologic conditions. Twenty-one healthy female volunteers received, in a randomized, double-blind, crossover study, celecoxib 200 mg twice a day, indomethacin 50 mg three times a day, or placebo for 4 days and a single dose, each, on day 5. On day 5 of each treatment, the following parameters were assessed with subjects in an upright position before and after administration of 20 mg furosemide intravenously: plasma renin activity (PRA), plasma aldosterone, serum and urine electrolytes, and creatinine. Index metabolites of prostanoids were analyzed by gas chromatography-tandem mass spectrometry in 24-hour urine on day 4 and in 2-hour urines before and after furosemide administration. Baseline and furosemide-stimulated PRA were reduced to a similar degree by celecoxib and indomethacin. Plasma aldosterone and urinary excretion of potassium showed changes consistent with the alteration of PRA. Urinary excretion rates of prostaglandin E(2), (PGE(2)), 7alpha-hydroxy-5, 11-diketotetranor-prosta-1,16-dioic acid (PGE-M), and 2,3-dinor-thromboxane B(2) (TxB(2)) were not reduced by celecoxib, whereas indomethacin led to a decrease of 40%, 45%, and 80%, respectively. Both active treatments inhibited urinary excretion of 2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha) by 60% and 40%, respectively. Renin-release in healthy humans with normal salt intake is COX-2 dependent. While COX-1 is critical for renal and systemic PGE(2) production, renal prostacyclin synthesis is apparently COX-2 dependent. Finally, the previously demonstrated shift of the thromboxane-prostacyclin balance toward prothrombotic thromboxane by specific COX-2 inhibition is confirmed.

Pharmacoscintigraphic evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans

Hollow microspheres (microballoons) floating on artificial gastric juice were developed as a floating controlled drug delivery system in the stomach. The intragastric behavior of 99mTc labelled microballoons (MB) and nonfloating microspheres (NF) (control) following oral administration in fasted and fed humans was investigated by gamma scintigraphy. Simultaneously, pharmacokinetic examination of riboflavin released from MB and NF was conducted in fasted and fed human subjects. In the fed state, MB were dispersed in the upper portion of the stomach; moreover, MB were retained in the stomach up to 300 min compared with NF, which descended gradually into the lower part of stomach within 90 min. In the fasted state, MB floated for approximately 60 min, after which it was removed rapidly via the cyclic activity referred to as the interdigestive migrating motor complex (IMMC). NF were removed more rapidly, i.e., within 60 min. Pharmacokinetic parameters, e.g., excretion half-life time ( t 1/2) and total urinary excretion, were well correlated with the gastric residence time (GRT) determined by the gamma scintigraphy analysis. The present investigation suggests that MB are very useful for improving drug bioavailability, resulting in a more sustained pharmacological action.

Steroid synthesis inhibition with ketoconazole and its effect upon the regulation of the hypothalamus-pituitary-adrenal system in healthy humans

Steroid synthesis inhibition with ketoconazole and its effect upon the regulation of the hypothalamus-pituitary-adrenal system in healthy humans

In vitro and in vivo evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans

Microballoons (MB) possessing a spherical cavity enclosed within a hard polymer shell have been developed as a dosage form characterized by excellent buoyancy in the stomach. MB were prepared by the emulsion solvent diffusion method using enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. Riboflavin-containing MB were administered orally to each of three healthy volunteers. The pharmacokinetics of riboflavin was investigated by analysis of the urinary excretion. Prolongation of the urinary excretion of riboflavin could be obtained by ingestion of water as well as “fed” conditions. This phenomenon was attributable to the buoyancy properties of MB in the stomach and an increase in the gastric residence time (GRT). The excretion half-life time ( t 1/2) following administration of MB (particle size: 500–1000 μm) exhibiting high buoyancy was longer than that of MB (particle size: <500 μm) displaying low buoyancy. Therefore, the intragastric floating properties of MB are potentially beneficial as far as a sustained pharmacological action is concerned. MB prepared by mixing it with hydroxypropylmethylcellulose (HPMC) in different ratio, results in improved riboflavin-release properties. These MB were evaluated in vivo by analysis of the urinary excretion of riboflavin. As a result, strong correlations were observed between the buoyancy and excretion half-life ( t 1/2) and between the riboflavin release from the MB and total urinary excretion.

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans.

Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease. However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic system, we measured intra-arterial blood pressure, arterial blood gases, systemic and skeletal muscle noradrenaline (norepinephrine) spillover and vascular conductances in nine Danish lowlanders at sea level and after 9 weeks of exposure at 5260 m. Mean blood pressure was 28 % higher at altitude (P < 0.01) due to increases in both systolic (18 % higher, P < 0.05) and diastolic (41 % higher, P < 0.001) blood pressures. Cardiac output and leg blood flow were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % (P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentrations were 3.7- and 2.4-fold higher at altitude, respectively (P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body NA release (P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NA spillover was increased similarly (x 3.2, P < 0.05). These changes occurred despite the fact that systemic O2 delivery was greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration. In summary, this study shows that chronic hypoxia causes marked activation of the sympathetic nervous system in healthy humans and increased systemic arterial pressure, despite normalisation of the arterial O2 content with acclimatisation.

Effects of aging and alterations in dietary sodium intake on total nitric oxide production

Animal studies suggest that nitric oxide (NO) deficiency is linked to salt-sensitive hypertension and that NO activity decreases during normal aging. This study investigates the impact of increasing age and manipulations in dietary salt intake on biochemical indices of the NO system in healthy humans. We measured NO2 + NO3 (NOx; stable oxidation products of NO) and cyclic guanosine monophosphate (cGMP; major second messenger) in plasma and urine of 30 healthy subjects aged 22 to 77 years. Subjects were maintained on controlled low NOx and low-, normal-, or high-salt diets for 3 days. Salt sensitivity of blood pressure was seen only in the oldest subjects. Plasma renin activity was suppressed by a high salt intake in all age groups, and baseline values declined with advancing age. Neither age nor salt intake correlated with indices of NO activity over the third 24-hour period of controlled salt intake. In a subgroup of subjects aged 33 ± 4 years challenged with ultrahigh sodium intake (400 mEq/24 h), again there was no increase in NO2 + N0 3 or cGMP measures. In contrast to animal studies, there is no correlation in humans between either salt intake or age and total NO production and activity, indicated by NO2 + N03 and cGMP measures. This does not preclude undetected alterations occurring in NO production and/or activity in strategic locations in the kidney and cardiovascular system. Limitations of blood and urine measurements of NO2 + N03 and cGMP as indices of NO activity are discussed.

Renal response to captopril reflects state of local renin system in healthy humans

Heightened activity of the renin-angiotensin system has been linked to the development of both essential hypertension and diabetic nephropathy. Blunting of the renal vasoconstrictor response to Ang II, specifically when it is corrected by angiotensin converting enzyme (ACE) inhibition, is a feature which we have employed as a marker for activation of the intrarenal RAS. In this study we tested the hypothesis that variation in the renal vasodilator response to ACE inhibition in healthy humans reflected the variation in angiotensin-mediated renal vasoconstriction provoked by a low-salt diet. We studied 20 healthy people (ages 19 to 57; 15 males) who were in balance on a low sodium diet. Ang II was infused for 45 minutes (3 ng/kg/min), followed by 25 mg captopril and a repeat Ang II infusion; PAH clearance was measured at the end of each interval. All subjects responded to captopril with a rise in renal plasma flow (range 43 to 242, mean 118 + 12 ml/min/1.73 m2). Individual vasodilator response to captopril was a strong inverse predictor of the precaptopril vasoconstrictor response to Ang II (P = 0.006, r = -0.59). There was a stronger, positive correlation of the vasodilator response to captopril and enhancement of Ang II responsiveness after captopril (r = 0.57). Plasma renin activity was significantly correlated with captopril response among the large responders (P = 0.003; r = 0.83), but not at all among those with little response. These results suggest substantial variation in angiotensin-mediated control of the renal circulation in healthy individuals on a low sodium intake. Variation in the vasodilator response to captopril, correlated with responses to Ang II, provides a measure of that control.

Effects of Pulsed High-Frequency Electromagnetic Fields on the Neuroendocrine System

The influence of pulsed high-frequency electromagnetic fields emitted from a circularly polarized antenna on the neuroendocrine system in healthy humans was investigated (900 MHz electromagnetic field, pulsed with 217 Hz, average power density 0.02 mW/cm²). Nocturnal hormone profiles of growth hormone (GH), cortisol, luteinizing hormone (LH) and melatonin were determined under polysomnographic control. An alteration in the hypothalamo-pituitary-adrenal axis activity was found with a slight, transient elevation in the cortisol serum level immediately after onset of field exposure which persisted for 1 h. For GH, LH and melatonin, no significant effects were found under exposure to the field compared to the placebo condition, regarding both total hormone production during the entire night and dynamic characteristics of the secretion pattern. Also the evaluation of the sleep EEG data revealed no significant alterations under field exposure, although there was a trend to an REM suppressive effect. The results indicate that weak high-frequency electromagnetic fields have no effects on nocturnal hormone secretion except for a slight elevation in cortisol production which is transient, pointing to an adaptation of the organism to the stimulus.