脑胆碱能刺激引起的促钠排泄反应和肾的ChAT-IR的变化

目的：观察肾胆碱能系统在大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（CBC）诱导的促钠排泄反应中的作用。方法：通过整体实验和免疫组化的方法观察大鼠侧脑室注射CBC 0.5μg后,肾排纳量的变化和肾的但碱乙酰转移酶（ChAT）免疫反应活性的变化;阿托品（30μg）阻断脑胆碱能M受体后,对上述效应的影响。结果：侧脑室给予CBC后40min,肾排钠量显著增加,肾近曲小管ChAT-IR显著增强（P〈0．05）;阿托品阻断后,上述反应显著减弱（P〈0．05）。结论：肾小管上皮细胞的胆碱能系统可能参与脑胆碱能刺激引起的肾促钠排泄反应。     

A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280-350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n?=?6) or free saporin (sham; 1.3 ng in 60 nl; n?=?7). Two weeks later, the rats were anesthetized (urethane 1.2 g?kg(-1) b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml?kg(-1) b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (-45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition.     

Impaired Pressure Natriuresis in Obese Youths

Objective: To compare the response and recovery of blood pressure (BP) and sodium excretion (U_NaV) in response to a behavioral stressor in overweight/obese and lean adolescents. Research Methods and Procedures: Twenty‐five lean (12% to 20% body fat) and 59 overweight/obese (>25% body fat) normotensive adolescents were provided all meals for 3 days (average sodium intake, 4000 ± 200 mg/d), before performing the stressor on the third day. There was a 2‐hour pre‐stress rest, followed by a 1‐hour stress (involving a video game task), and a 2‐hour recovery. Percentage of body fat was obtained from DXA. U_NaV was measured hourly, whereas systolic BP and diastolic BP measurements were obtained at 15‐minute intervals, and averaged for each 1‐hour period. Results: There was no significant difference between the lean and overweight/obese group for the response of systolic BP and diastolic BP (group by time interaction, p = 0.60 and p = 0.64, respectively). However, the lean group had a significantly greater increase in U_NaV in response to the stressor compared with the overweight/obese group (p = 0.02). U_NaV remained elevated compared with baseline in both groups at the 1‐hour (p ≤ 0.0001) and 2‐hour (p ≤ 0.0001) post‐time points. Furthermore, there was a tendency for a larger number of sodium retainers in the overweight/obese group compared with the lean group (39.0% vs. 20.0%; χ² = 2.85, df = 1, p = 0.09). Discussion: This study provided evidence that sodium regulation was impaired during a behavioral stress in overweight/obese individuals compared with lean individuals.     

Eye movements induced by linear acceleration in humans.

The otolith-function study is remarkably behind the semicanal-function study. In the present paper, we introduced briefly our on-going studies on eye movements including nystagmic elicitation during lateral (Gy) linear acceleration with step and sinusoidal modes using a sled-type accelerator. The eye movements were recorded by EOGs (DC) from subjects who looked at an imaginary target of their straight ahead in darkness during G-loading up to 0.5 G. Corresponding to the +Gy and -Gy segments, nystagmus and/or deviation in eye position were frequently induced in some subjects, but none or slightly in the other. The nystagmus changed the beating direction dependently on the Gy direction, while the eye-deviation could be either direction of compensatory or anticompensatory. In half of subjects, nystagmus elicitation was absent or low at 0.3 G, while it tended to increase above 0.3 G. The nystagmic elicitation was similar to each other between the both modes of acceleration, and directional preponderance (DP) was observed in some subjects. There was no correlation between the DP and the nystagmic slow-phase velocity. Functional meanings of these findings were discussed.     

Changes in respiratory activity induced by mastication in humans.

We studied the influence of mastication on respiratory activity in nine healthy volunteers who were requested to masticate a 5-g chewing gum bolus at a spontaneous rate (SR) for 5 min and "at the maximum possible rate" (MPR) for 1 min. Significant increases in respiratory frequency were induced by SR mastication due to a decrease in both the inspiratory and expiratory time. Tidal volume displayed slight nonsignificant decreases, but minute ventilation and mean inspiratory flow significantly increased. The duty cycle (TI/TT) did not change significantly. Total airway resistance significantly increased. Both peak and rate of rise of the integrated electromyographic activity of inspiratory muscles presented marked increases, accompanied by the appearance of a low level of tonic muscular activity. Similar but more intense effects on respiratory activity were induced by MPR mastication; in addition, a significant decrease in tidal volume and a significant increase in TI/TT were observed. Rhythmic handgrip exercise performed at metabolic rates comparable to those attained during SR or MPR mastication induced similar changes in the drive and time components of the breathing pattern, although accompanied respectively by nonsignificant or significant increases in tidal volume. Furthermore, the frequency of SR mastication significantly entrained the respiratory rhythm. The results suggest that mastication-induced hyperpnea does not merely represent a ventilatory response to exercise but also reflects complex interactions between respiratory and nonrespiratory functions of the upper airway and chest wall muscles.     

Metabolic disruptions induced by reduced ambulatory activity in free-living humans

Physical inactivity likely plays a role in the development of insulin resistance and obesity; however, direct evidence is minimal and mechanisms of action remain unknown. Studying metabolic outcomes that occur after transitioning from higher to lower levels of physical activity is the best tool to answer these questions. Previous studies have successfully used more extreme models of inactivity, including bed rest, or the cessation of exercise in highly trained endurance athletes, to provide novel findings. However, these models do not accurately reflect the type of inactivity experienced by a large majority of the population. Recent studies have used a more applicable model in which active (～10,000 steps/day), healthy young controls are asked to transition to an inactive lifestyle (～1,500 steps/day) for a 14-day period. The transition to inactivity resulted in reduced insulin sensitivity and increased central adiposity. This review will discuss the outcomes of these studies, their implications for the cause/effect relationship between central adiposity and insulin resistance, and provide rationale for why inactivity induces these factors. In addition, the experimental challenges of directly linking acute responses to inactivity to chronic disease will also be discussed.     

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cortical activation induced by intraoral stimulation with water in humans

Studies of gustatory processing frequently utilize water as a control stimulus. However, the neural representations of intraoral stimulation with water have received little attention. We report a series of positron emission tomography studies involving intraoral stimulation with deionized distilled water. Attempting to taste water produced large, bilateral activations in insular, opercular, Rolandic and cerebellar cortices relative to resting with eyes closed or 'smelling' odorless air. The magnitude and volume of activation was substantially reduced when tasting water was contrasted with voluntary swallowing. This indicates that much of the activity induced by water reflects intraoral somatosensory or motor processing. Nevertheless, portions of the insula, operculum, post-central gyrus and cerebellum remained significantly activated in the contrast between 'tasting' water and swallowing. This activity appears to represent a specific neural correlate of fluid stimulation, and may reflect aspects of trigeminal, gustatory or thermal coding. These findings emphasize the large volume of cortex dedicated to intraoral processing, and highlight the importance of controlling for nongustatory factors in studies of gustation.     

Skin temperature changes in humans induced by local peripheral cooling

Local peripheral cooling (immerson of legs up to the knees into 12°C water) increased heart rate and blood pressure by 10–20% within the first 3–10 min of cooling. During further cooling heart rate remained elevated, while systolic and diastolic blood pressures decreased to the control value. Data on heart rate indicate a permanent activation of the sympathetic nervous system during local cooling.Skin temperatures (measured topically by thermosensors) decreased on some non-cooled areas of the body (fingers, palms and thighs) immediately after the start of local cooling. On the other hand, skin temperatures on chest and forehead were not influenced. During cooling skin temperatures on thighs remained low, but skin temperatures on fingers tended to increase. Changes in skin temperatures on non-cooled areas of the body indicate that a permanent and generalized activation of the sympathetic nervous system occurs during local cooling.Cold induced cycles of vasodilation (CIVD) were observed on fingers, palms and forearms during local cooling. Minute cycles in skin temperatures were observed on forehead, thighs and chest. Minute cycles coincided with those in the heart rate, indicating a permanent, generalized but discontinuous control of vasomotion by the sympathetic nervous system during local cooling.Infrared thermographic recordings from different body areas indicated that local peripheral cooling lowered skin temperatures in all areas of the body within 5 min. Distant areas of the body (extremities) and pectoral muscles showed greater hypothermia than abdominal areas and head. After 10 min of cooling average skin temperatures in all areas of the body returned to the original level and further fluctuated at approximately 10–15 min intervals.Data indicate that during local cooling skin blood flow in all areas of the body surface permanently fluctuates forming a mosaic of dynamic changes in skin temperatures. Since tympanic temperature increases, while skin temperature decreases immediately after the start of the local cooling, it appears that the initial vasoconstrictor response is being controlled independently of the central temperature input.     

Atrial distension in humans during weightlessness induced by parabolic flights

Central venous pressure, esophageal pressure, and left atrial diameter were measured in individuals during each stage of parabolic flight, with emphasis on weightlessness. Results indicated that short periods of weightlessness lead to an increase in transmural central venous pressure and left atrial diameter, although there is a decrease in central venous pressure.     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

Cholecystokinin pathways modulate sensations induced by gastric distension in humans

Ingested fat releases CCK, causes gastric relaxation, delays gastric emptying, and limits meal size; however, the mechanistic link among these actions has not been established. Fatty acid release of CCK is chain-length sensitive; dodecanoic acid (C12) induces greater CCK release than decanoic acid (C10). The effect of C12 or C10 on tolerance to subsequent intragastric infusion of liquid was determined in healthy subjects, with and without the CCK(1) receptor antagonist dexloxiglumide. Gastric wall relaxation after either fatty acid was assessed by graded volume distension and by barostat; gastric emptying was measured by gastric aspiration and by a [(13)C]octanoic acid breath technique. C12 released more CCK (mean plasma CCK after vehicle, 4.7 +/- 0.8 pM; C10, 4.8 +/- 0.3 pM; C12, 8 +/- 1.2 pM; P < 0.05 C12 vs. C10 or vehicle) and reduced the volume of water (and of 5 and 25% glucose solutions) delivered at maximum tolerance compared with C10 or vehicle (volume of water tolerated after vehicle, 1,535 +/- 164 ml; C10, 1,335 +/- 160 ml; C12, 842 +/- 103 ml; P < 0.05 C12 vs. C10 or vehicle); this effect was abolished by dexloxiglumide. Intragastric volumes were always similar at the limit of tolerance, and, whereas gastric relaxation occurred to similar degrees after the fatty acids, its duration was longer after C12, which also induced a longer delay in half-gastric emptying [t(1/2)(min) after vehicle, 53 +/- 2; C10, 67 +/- 3; C12, 88 +/- 7; P < 0.05 C12 vs. C10 or vehicle]. In conclusion, ingestion of a CCK-releasing fatty acid reduces the tolerated volume of liquid delivered into the stomach, primarily via a CCK(1) receptor-mediated delay in gastric emptying.     

Tolerance to morphine induced by chronic mild environmental stressors

Pain-sensitivity as well as the analgesic and thermoregulatory effects of morphine were studied after two different types of chronic environmental stresses in rats (extra stimulation of newborns for 21 days, or social isolation for a month in adult age). The basal pain sensitivity and the base-line body temperature were similarly affected after the two interventions: an increased tail-flick latency, a decreased hot-plate latency and a decreased body temperature were noted. The analgesic and thermoregulatory effects of morphine were uniformly reduced in rats exposed to either stress. These findings suggest a common effect of various non painful mild environmental stresses on the activity of the endogenous opioid system.     

Thermoregulatory changes in the cold induced by physical training in humans

It has previously been demonstrated that metabolic heat production (M˙) during cold exposure at rest was related to maximal oxygen uptake (O_2max). Consequently, an increase in O_2max could allow an increase M˙ in the cold. The aim of the present study was therefore to test this hypothesis. Eight male volunteers undertook interval training (periods of 25% V˙O_2max of 30-s duration and 110% V˙O_2max of 60-s duration until exhaustion, five times a week over 8 weeks) to increase V˙O_2max. Both before and after this physical training, they were subjected to a 10^∘, 5^∘ and 1^∘C 2-h cold air test in a climatic chamber. During the cold exposure, rectal temperature (T _re), tympanic temperature (T _ty), mean skin temperature () and M˙ were measured as well as the time to onset of shivering (t) and body temperatures () at t. The results showed that physical training involved an increase in O_2max (14%–15%, P < 0.05). During the cold exposure, T _re was higher after training both at 10^∘,5^∘ and 1^∘C (P < 0.05) whereas were not significantly changed. However, an increase in the sensitivity of the thermoregulatory system was attested by a decreased t at higher These slight physiological changes found after training were not related to the increases in V˙O_2max. In conclusion, this study demonstrated that interval training induced slight thermoregulatory changes unrelated to changes in V˙O_2max and it suggested that M˙ during cold exposure could be related mainly to the level of V˙O_2max observed before training, since increases in V˙O_2max did not modify M˙. Accepted: 8 April 1998     

Peripheral blood flow during rewarming from mild hypothermia in humans

During the initial stages of rewarming from hypothermia, there is a continued cooling of the core, or after-drop in temperature, that has been attributed to the return of cold blood due to peripheral vasodilatation, thus causing a further decrease of deep body temperature. To examine this possibility more carefully, subjects were immersed in cold water (17 degrees C), and then rewarmed from a mildly hypothermic state in a warm bath (40 degrees C). Measurements of hand blood flow were made by calorimetry and of forearm, calf, and foot blood flows by straingauge venous occlusion plethysmography at rest (Ta = 22 degrees C) and during rewarming. There was a small increase in skin blood flow during the falling phase of core temperature upon rewarming in the warm bath, but none in foot blood flow upon rewarming at room air, suggesting that skin blood flow seems to contribute to the after-drop, but only minimally. Limb blood flow changes during this phase suggest that a small muscle blood flow could also have contributed to the after-drop. It was concluded that the after-drop of core temperature during rewarming from mild hypothermia does not result from a large vasodilatation in the superficial parts of the periphery, as postulated. The possible contribution of mechanisms of heat conduction, heat convection, and cessation of shivering thermogenesis were discussed.     

Arterial pressure in humans during weightlessness induced by parabolic flights.

Results from our laboratory have indicated that, compared with those of the 1-G supine (Sup) position, left atrial diameter (LAD) and transmural central venous pressure increase in humans during weightlessness (0 G) induced by parabolic flights (R. Videbaek and P. Norsk. J. Appl. Physiol. 83: 1862-1866, 1997). Therefore, because cardiopulmonary low-pressure receptors are stimulated during 0 G, the hypothesis was tested that mean arterial pressure (MAP) in humans decreases during 0 G to values below those of the 1-G Sup condition. When the subjects were Sup, 0 G induced a decrease in MAP from 93 +/- 4 to 88 +/- 4 mmHg (P < 0.001), and LAD increased from 30 +/- 1 to 33 +/- 1 mm (P < 0.001). In the seated position, MAP also decreased from 93 +/- 6 to 87 +/- 5 mmHg (P < 0.01) and LAD increased from 28 +/- 1 to 32 +/- 1 mm (P < 0.001). During 1-G conditions with subjects in the horizontal left lateral position, LAD increased compared with that of Sup (P < 0.001) with no further effects of 0 G. In conclusion, MAP decreases during short-term weightlessness to below that of 1-G Sup simultaneously with an increase in LAD. Therefore, distension of the heart and associated central vessels during 0 G might induce the hypotensive effects through peripheral vasodilatation. Furthermore, the left lateral position in humans could constitute a simulation model of weightlessness.