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Central thermal adaptation of lower brain stem units in the guinea-pig.

Cold adaptive changes were found in single units responding to thermal skin stimulation. All units were located in the subcoeruleus region of the lower brain stem. In cold-adapted guinea-pigs (five weeks in ambient temperature of 4 degrees C), the maximum activity of cold-responsive neurones was reduced markedly in comparison with that of cold-responsive neurones in animals adapted to room temperature (ca. 21 degrees C). This decrease may be a neuronal correlate to long-term downward shifts of shivering threshold temperature known to occur within adaptation periods of several weeks in man, as well as in animals.

Acclimatization↗

The initial responses to cold-water immersion in man.

This review is summarized in Fig. 1. It is concluded that the cold-shock response can result in the death or serious incapacitation of an individual long before general hypothermia develops. As such, this response is probably responsible for the majority of annual open-water immersion deaths.

Cardiovascular System↗

Mutations in the Ca2+/H+ transporter CAX1 increase CBF/DREB1 expression and the cold-acclimation response in Arabidopsis.

Transient increases in cytosolic free calcium concentration ([Ca2+]cyt) are essential for plant responses to a variety of environmental stimuli, including low temperature. Subsequent reestablishment of [Ca2+]cyt to resting levels by Ca2+ pumps and antiporters is required for the correct transduction of the signal [corrected]. C-repeat binding factor/dehydration responsive element binding factor 1 (Ca2+/H+) antiporters is required for the correct transduction of the signal. We have isolated a cDNA from Arabidopsis that corresponds to a new cold-inducible gene, rare cold inducible4 (RCI4), which was identical to calcium exchanger 1 (CAX1), a gene that encodes a vacuolar Ca2+/H+ antiporter involved in the regulation of intracellular Ca2+ levels. The expression of CAX1 was induced in response to low temperature through an abscisic acid-independent pathway. To determine the function of CAX1 in Arabidopsis stress tolerance, we identified two T-DNA insertion mutants, cax1-3 and cax1-4, that display reduced tonoplast Ca2+/H+ antiport activity. The mutants showed no significant differences with respect to the wild type when analyzed for dehydration, high-salt, chilling, or constitutive freezing tolerance. However, they exhibited increased freezing tolerance after cold acclimation, demonstrating that CAX1 plays an important role in this adaptive response. This phenotype correlates with the enhanced expression of CBF/DREB1 genes and their corresponding targets in response to low temperature. Our results indicate that CAX1 ensures the accurate development of the cold-acclimation response in Arabidopsis by controlling the induction of CBF/DREB1 and downstream genes.

Abscisic Acid↗

Impairment of coronary microvascular dilation in response to cold pressor--induced sympathetic stimulation in type 2 diabetic patients with abnormal stress thallium imaging.

Coronary microcirculation dysfunction may be associated with myocardial perfusion defects on thallium imaging in diabetic patients without coronary artery stenosis. Microvascular coronary adaptation to increased myocardial oxygen demand in response to sympathetic stimulation evoked by the cold pressor test was examined in 22 type 2 diabetic patients with thallium imaging defects and in 15 control subjects. Both the diabetic patients and control subjects had angiographically normal coronary arteries and no other risk factors. Despite a similar increase in the rate-pressure product in the two groups (22.6 +/- 12.4% in diabetic patients and 31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in the left anterior descending artery (mean flow velocity measured by intracoronary Doppler multiplied by the cross-sectional area measured by digital angiography) was significantly lower in diabetic patients than in control subjects (14.7 +/- 19.8 vs. 75.5 +/- 13.5%, respectively; P = 0.0001). In addition, when there was a positive correlation between the two parameters in control subjects (r = 0.651, P < 0.01), there was no relationship in diabetic patients (r = 0.054). In conclusion, vasodilation of the coronary microcirculation in response to sympathetic stimulation evoked by the cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilation during current life stress episodes such as exercise, mental stress, or cold exposition.

Blood Flow Velocity↗

Heat production and body temperature during cooling and rewarming in overweight and lean men.

OBJECTIVE: To compare overweight and lean subjects with respect to thermogenesis and physiological insulation in response to mild cold and rewarming. RESEARCH METHODS AND PROCEDURES: Ten overweight men (mean BMI, 29.2 +/- 2.8 kg/m(2)) and 10 lean men (mean BMI, 21.1 +/- 2.0 kg/m(2)) were exposed to cold air for 1 hour, followed by 1 hour of rewarming. Body composition was determined by hydrodensitometry and deuterium dilution. Heat production and body temperatures were measured continuously by indirect calorimetry and thermistors, respectively. Muscle activity was recorded using electromyography. RESULTS: In both groups, heat production increased significantly during cooling (lean, p = 0.004; overweight, p = 0.006). The increase was larger in the lean group compared with the overweight group (p = 0.04). During rewarming, heat production returned to baseline in the overweight group and stayed higher compared with baseline in the lean group (p = 0.003). The difference in heat production between rewarming and baseline was larger in the lean (p = 0.01) than in the overweight subjects. Weighted body temperature of both groups decreased during cold exposure (lean, p = 0.002; overweight, p < 0.001) and did not return to baseline during rewarming. DISCUSSION: Overweight subjects showed a blunted mild cold-induced thermogenesis. The insulative cold response was not different among the groups. The energy-efficient response of the overweight subjects can have consequences for energy balance in the long term. The results support the concept of a dynamic heat regulation model instead of temperature regulation around a fixed set point.

Adult↗

Thermoregulatory responses to cold water at different times of day.

This study examined how time of day affects thermoregulation during cold-water immersion (CWI). It was hypothesized that the shivering and vasoconstrictor responses to CWI would differ at 0700 vs. 1500 because of lower initial core temperatures (T(core)) at 0700. Nine men were immersed (20 degrees C, 2 h) at 0700 and 1500 on 2 days. No differences (P > 0.05) between times were observed for metabolic heat production (M, 150 W. m(-2)), heat flow (250 W. m(-2)), mean skin temperature (T(sk), 21 degrees C), and the mean body temperature-change in M (DeltaM) relationship. Rectal temperature (T(re)) was higher (P < 0.05) before (Delta = 0.4 degrees C) and throughout CWI during 1500. The change in T(re) was greater (P < 0. 05) at 1500 (-1.4 degrees C) vs. 0700 (-1.2 degrees C), likely because of the higher T(re)-T(sk) gradient (0.3 degrees C) at 1500. These data indicate that shivering and vasoconstriction are not affected by time of day. These observations raise the possibility that CWI may increase the risk of hypothermia in the early morning because of a lower initial T(core).

Adult↗

Thermal, osmotic and chemical modulation of neural activity in the paraventricular nucleus: in vitro studies.

To investigate the functions of the paraventricular nucleus (PVN) which plays an important role as an integration site for the neuroendocrine and autonomic nervous systems, the firing activity of PVN neurons was recorded from hypothalamic slice preparations during thermal, osmotic and chemical stimulation. Neurons responded to environmental factors such as temperature and osmolarity and both warm-responsive and cold-responsive neurons were observed in the PVN. Some PVN neurons were also osmoresponsive and unlike neurons in the supraoptic nucleus, most osmoresponsive PVN neurons decreased their firing rate during hyperosmotic stimulation. One of the classical transmitters, noradrenaline, exerted excitatory effects on PVN neurons through alpha 1- and beta-receptors and inhibitory responses through alpha 2-receptors. Atrial natriuretic polypeptide exerted inhibitory effects on putative parvocellular PVN neurons but it had no effect on putative magnocellular PVN neurons. An endogenous sugar derivative, 2-deoxytetronic acid, thought to be an endogenous satiety factor, elicited inhibitory effects, supporting the possibility that the PVN also may be related to feeding behaviour. Arginine-vasopressin and oxytocin which are synthesised in the magnocellular neurosecretory cells excited PVN neurons, suggesting that the PVN may have short circuits modulating neural activity within the nucleus itself. We conclude that neurons in the PVN may receive multiple information and act as one of the important integrative sites in the brain.

Action Potentials↗

The bronchial response to cold air challenge: evidence for different mechanisms in normal and asthmatic subjects.

We have investigated possible mechanisms of response to airway cooling by studying the effects of sodium cromoglycate and ipratropium bromide on the changes in airways resistance that followed eucapnic hyperventilation with subfreezing air in a group of 12 patients with mild asthma and 10 normal subjects. We have also studied the period of refractoriness to repeated challenge. Maximum bronchoconstriction was not reduced after the second challenge, but in the asthmatics the one-second forced expiratory volume recovered more rapidly after the second challenge. The response in normal subjects was completely abolished by ipratropium bromide (p less than 0.0005) whereas sodium cromoglycate was without effect. In the asthmatics both ipratropium and cromoglycate were effective in attenuating the response (p less than 0.005). These results suggest that in normal subjects the response to airway cooling is produced predominantly via neural mechanisms, whereas in asthmatics there is an additional mechanism which can be abolished by sodium cromoglycate.

Adolescent↗

Isolation of cold stress-responsive genes in the reproductive organs, and characterization of the OsLti6b gene from rice (Oryza sativa L.).

During their reproductive stage, rice crops often are exposed to cold stress, which leads to sterility and reduced yields. To understand the cold response mechanism at that stage, we used an mRNA differential display method to isolate cold-responsive genes from pre-anthesis flowers. Approximately 5,000 transcripts were identified here, of which 123 were found to be displayed differentially between the control (30 degrees C) and cold-treated (12 degrees C) flowers. Among them, 26 were analyzed by northern analysis; 8 of those clones were confirmed as cold-responsive. OsLti6b, encoding a hydrophobic protein homologous to Arabidopsis RCI2, was analyzed in detail. RNA blot analysis revealed that its transcript is increased by cold, salt, drought, or ABA treatments. In situ hybridization indicated that this transcript is highly accumulated in the ovaries and stamens of cold-treated flowers, particularly in the anther walls and vascular tissues of the filaments. Over-expression of OsLti6b increased cold tolerance as revealed by seedling wilting rates and ion leakages of mature leaves, demonstrating that the extent of the tolerance correlates well with its expression level.

Cold Temperature↗

Acupuncture effects on autonomic responses to cold pressor and handgrip exercise in healthy humans.

Acupuncture at P6, Liv 3 and Li 4 attenuates the increase in blood pressure during mental stress in healthy humans. The purpose of this study was to test the hypothesis that acupuncture at these points has a generalized depressor effect seen during other stimuli to the autonomic nervous system. Thirty-eight healthy humans (mean age 33 +/- 13 years) performed handgrip exercise (n = 20) or the cold pressor test (n = 18) before and after acupuncture at P6, Liv 3 and Li4. To control for repeated interventions, subjects underwent an identical protocol on a different day, during which acupuncture was replaced by quiet rest. Blood pressure and heart rate increased similarly during the first and repeat intervention (handgrip or cold pressor test). Acupuncture did not attenuate the increase in blood pressure (delta mean arterial pressure [MAP] 9.3 +/- 1.8 vs 7.3 +/- 3.1 mmHg) or the increase in heart rate (delta heart rate [HR] 6.7 +/- 2.1 vs 6.0 +/- 2.0 bpm) during handgrip exercise. Similarly, acupuncture did not attenuate the increase in blood pressure (delta mean arterial pressure [MAP] 14.8 +/- 5.0 vs 14.8 +/- 4.8 mmHg) or the increase in heart rate (delta heart rate [HR] 5.3 +/- 2.1 vs 8.7 +/- 3.6 bpm) during the cold pressor test. In summary, in normal healthy humans, acupuncture at P6, Liv 3 and Li 4 does not attenuate the blood pressure or heart rate responses during handgrip exercise or the cold pressor test.

Acupuncture↗

Corticotropin-releasing hormone mediates the response to cold stress in the neonatal rat without compensatory enhancement of the peptide's gene expression.

A variety of stressors activate the hypothalamic-pituitary-adrenal axis, with secretion and compensatory enhanced synthesis of hypothalamic corticotropin-releasing hormone (CRH). Whether CRH is a major effector in the stress response of the neonatal rat and whether the peptide's gene expression is subsequently up-regulated are not fully understood. We studied the effect of cold-separation stress on plasma corticosterone (CORT) levels and CRH messenger RNA (CRH-mRNA) abundance in the paraventricular nucleus. Rats (4-16 days old) were subjected to maximal tolerated cold-separation. CORT and CRH-mRNA abundance were measured before and at several time points after stress. Cold-separation stress resulted in a significant plasma CORT increase in all age groups studied. This was abolished by the administration of an antiserum to CRH on both postnatal days 6 and 9. CRH-mRNA increased in rats aged 9 days or older, but not in 6-day-old rats, by 4 h after stress. These results suggest the presence of robust CRH-mediated adrenal responses to cold-separation stress in neonatal rats. Before postnatal day 9, however, the compensatory increase in CRH-mRNA abundance is minimal.

Adaptation, Physiological↗

Cold shock response in Bacillus subtilis.

Following a rapid decrease in temperature, the physiology of Bacillus subtilis cells changes profoundly. Cold shock adaptation has been monitored at the level of membrane composition, adjustment in DNA topology, and change in cytosolic protein synthesis/composition. Some major players in these processes (cold-stress induced proteins and cold acclimatization proteins, CIPs and CAPs) have been identified and mechanisms in cold shock acclimatization begin to emerge; however, important questions regarding their cellular function still need to be answered.

Bacillus↗

[Hormonal regulation of reproductive function in rats in response to cold stress in a context of chronic toluene poisoning].

Chronic toluene inhalation at a maximum permissible concentration (MPC) and 10-fold higher as well as cold stress result in a significant rise of blood prolactin in female rats. Cold stress in control animals causes a decrease in the level of gonad-releasing hormone (Gn-RH) in the hypothalamus. When exposed to toluene this reaction disappears. In 4 hours after estradiol administration control animals demonstrate an increase in the level of Gn-RH in the vascular organ of an end plate. Rats, exposed to toluene (in MPC concentration) and cold stress show a decrease in the level of hypothalamic Gn-RH. At a higher concentration of toluene the level of Gn-RH in the hypothalamus remains unchanged either after estradiol administration or in cold stress. Thus chronic toluene inhalation even at small concentrations changes hypothalamic reactivity in response to stress and hormonal stimuli.

Administration, Inhalation↗

Effects of passive heat adaptation and moderate sweatless conditioning on responses to cold and heat.

Two series of experiments were performed in physically untrained subjects. In series A (heat adaptation, HA), seven male subjects were adapted to dry heat (five consecutive days at 55 degrees C ambient air temperature (Ta) for 1 h X day-1) under resting conditions. Before and after HA, the subjects' shivering responses were determined in a cold test (Ta + 10 to 0 degrees C). In series B, eight male subjects underwent mild exercise training (five consecutive days at a heart rate, HR, of 120 b X min-1) under Ta conditions individually adjusted (Ta + 15 to +5 degrees C) to prevent both sweating and cold sensations. Before and after "sweatless training", the subjects were subjected to a combined cold and heat test. During HA the thresholds for shivering, cutaneous vasodilatation (thumb and forearm) and sweating were shifted significantly (p less than 0.05) towards lower mean body temperatures (Tb). The mean decrease in threshold Tb was 0.36 degrees C. "Sweatless training" resulted in a mean increase in work rate (at HR 120 b X min-1) and oxygen pulse of 13 and 8%, respectively. However, "sweatless training" did not change the threshold Tb for shivering or sweating. Neither HA nor "sweatless training" changed the slopes of the relationships of shivering and sweating to Tb. It is concluded that the previously reported lowering of shivering and sweating threshold Tb in long-distance runners is not due to an increased fitness level, but is essentially identical with HA. The decreased shivering threshold following HA is interpreted as "cross adaptation" produced by the stressors cold and heat.

Adaptation, Physiological↗

Genetic, acclimatizational and anthropometric factors in hand cooling among North and South Chinese.

The left hands of unacclimatized North Chinese (N=16) and South Chinese (N=13) were exposed to 5 degrees C water for 30 minutes followed by a 10 minute recovery period. Significant differences independent of body composition were found between the two samples on mean 30 minute temperature during immersion, time and temperature of the onset of initial CIVD (cold-induced vasodilation) at 0.01, 0.05 and 0.10 levels respectively. The result suggests the presence of a genetic component in the cold responses of Continental Asian populations and the possibility of the presence of a clinal distribution of cold response in Asia.

Acclimatization↗

Effects of bombesin on thermoregulatory responses and hypothalamic neuronal activities in the rat.

Direct administration of bombesin (1, 10, and 100 ng/microliter) into the preoptic anterior hypothalamic area caused a dose-related fall in rectal temperature at ambient temperatures (Ta) of 8 and 22 degrees C. The hypothermia in response to bombesin was brought about by a decrease in metabolism at Ta 8 degrees C, whereas at Ta 22 degrees C the hypothermia was brought about by both a decrease in metabolism and an increase in cutaneous temperature. However, at Ta 30 degrees C, intrahypothalamic administration of bombesin caused an insignificant change in thermoregulatory responses. On the other hand, 51 single neurons in the preoptic anterior hypothalamic area were examined in 20 rats under urethan anesthesia. Each animal was subjected to scrotal warming or cooling and to the administration of bombesin. Microiontophoretic application of bombesin resulted in inhibition of the majority (62.5%) of cold-responsive neurons as well as excitation of the majority (50%) of warm-responsive neurons recorded in the preoptic anterior hypothalamic area. However, the majority (74%) of thermally unresponsive neurons were not affected by bombesin application. The data indicate that bombesin, when administered intrahypothalamically, excites warm-responsive neurons and inhibits cold-responsive neurons within the preoptic anterior hypothalamic area to induce hypothermia by promoting an increase in heat loss and a decrease in heat production.

Animals↗