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Ventilatory and metabolic responses to cold and hypoxia in conscious rats with discrete hypothalamic lesions.

We tested the hypothesis that hypothalamic nuclei involved in thermoregulatory control could represent a site of integration of the metabolic and ventilatory response to cold and hypoxia. Electrolytic lesions were performed bilaterally under stereotaxic guide, either within the anterior or posterior hypothalamic areas of adult rats. One week later, oxygen consumption (VO2) and ventilation (VE) were measured in the conscious animals during warm (27 degrees C) or cold (12 degrees C) conditions, in normoxia (21% O2) or hypoxia (10% O2), and compared to measurements obtained in control rats, which were either intact or sham-operated. VO2, VE, and body temperature did not differ between lesioned and control rats during warm normoxia. In cold and hypoxia, singly or combined, VE/VO2 was higher in the lesioned rats, because of higher VE. The differences in the cold were mostly confined to rats with anterior lesions, whereas differences in hypoxia were mostly in rats with posterior lesions. We conclude that the integrity of the anterior and posterior hypothalamic areas is important for the proper coupling of metabolism and ventilation during cold or hypoxic stimuli.

Animals↗

Neuroendocrine response to cold in Raynaud's syndrome.

Eleven patients with Raynaud's syndrome accompanied by monospecific IgG ANA, nine patients with Raynaud's syndrome in the absence of ANA, and nine normal volunteers were exposed to an ambient cold challenge during which time venous blood was continuously sampled. ANA negative patients were shown to have significantly higher levels of cortisol during a cold challenge than either ANA positive patients or normal controls, and exhibited significantly lower levels of plasma norepinephrine compared with normal controls. ANA positive patients did not differ significantly from normals in their neuroendocrine response to cold. It is suggested that the high plasma cortisol found in Raynaud's syndrome in the absence of ANA may be responsible for the vasospasticity in this group of patients.

Antibodies, Antinuclear↗

The effect of indomethacin on the circulatory and plasma noradrenaline responses to cold pressor testing in normal subjects.

Prostaglandins may alter neuronal noradrenaline release or vascular responsiveness to sympathoexcitation. The purpose of this study was to determine if indomethacin, a prostaglandin synthesis inhibitor, influences the sympathetic and circulatory adjustments to a commonly utilized laboratory stressor in the clinical assessment of autonomic function, the cold pressor test. Venous plasma noradrenaline levels (n = 8), mean arterial pressure and heart rate (n = 10) were measured in healthy male subjects during immersion of the non-dominant hand in cold water (1 degree C) for 90 s. The subjects were given either placebo or indomethacin (100 mg) in a double-blind manner. The order of administration was counterbalanced and a 1 week period was given for systemic clearance of the drug. The absolute level of mean arterial pressure was elevated during the resting control period after indomethacin treatment (88 in placebo vs. 92 mmHg in indomethacin). Both heart rate and venous plasma noradrenaline levels were similar between trials during the resting control period. Mean arterial pressure and heart rate increased similarly during cold pressor testing in both indomethacin and placebo. Venous plasma noradrenaline levels increased during cold pressor testing 162 +/- 39 vs. 200 +/- 69 pg/ml in indomethacin vs. placebo (p > 0.05), respectively. In addition, perceived pain (peak level = 7 +/- 1 vs. 6 +/- 1 units; indomethacin vs. placebo, respectively) was not different between the trials. These results suggest that administration of indomethacin in a maximal single therapeutic dose, does not affect the sympathetic nervous system or circulatory responsiveness to cold pressor testing. It may not be necessary to discontinue indomethacin prior to autonomic function testing.

Adult↗

Response properties of primary somatosensory cortical neurons responsive to cold stimulation of the facial skin and oral mucous membrane.

The distribution and response characteristics of the primary somatosensory cortical (SI) neurons activated by cold stimulation of the facial skin and oral mucous membrane were studied in cats. The discharge activities of 53 cold-sensitive SI neurons that responded to a decrease in temperature of the facial skin and/or oral mucous membrane were recorded. Each of these neurons was classified according to its responsiveness to mechanical stimulation as follows: LTM (low-threshold mechanoreceptive, 14/53), WDR (wide dynamic range, 39/53) and NS (nociceptive-specific, none identified). Encoding and non-encoding SI cold-sensitive neurons were identified, according to their responsiveness to decremental thermal stimulation. Only 14 cold-sensitive SI neurons demonstrated increased firing frequencies when subjected to incremental stimulus intensity increases and were classified as the encoding-type, whereas 39 non-encoding-type neurons did not.

Animals↗

Ethanol effect on activation and maintenance of cold stress response in immature rats.

Rats at thermoneutral ambient temperature (Ta) exhibit change in thermoregulatory response to ethanol (EtOH) from 2 to 15 days of age. In the present study, rats at 2-3, 8-9, and 14-15 days of age were administered either saline or EtOH (4 g/kg b.wt.;IP) using two different routines to determine EtOH effect on specific cold defense mechanisms. Injection of EtOH in the first routine occurred after exposure to cold Ta, to determine effect on maintenance of cold thermogenesis. EtOH-induced metabolic depression increased from 3 to 8 days of age, with little change after this time. Injection of EtOH in the second routine was at thermoneutral Ta, followed at 20 min postinjection by rapid exposure to cold Ta to determine effect on activation of cold thermogenesis. EtOH-treatment delayed onset of cold thermogenesis at 2-3 and 14-15 days of age, and completely eliminated 8-9-day-old response to cold Ta. Rats exposed to cold Ta at 2-3 days of age exhibited a slower rate of EtOH absorption and lower blood EtOH concentration than rats in the older groups, to explain some age differences in EtOH response.

Animals↗

Further evidence of the dual role of noradrenaline in regulation of thyrotrophin secretion in male rats.

The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. Alpha-Methyl-p-tyrosine (alpha MPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5-6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of L-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of alpha MPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by L-dopa (which restores DA levels). DOPS even potentiated the depressive effect of alpha MPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.

Animals↗

Control of metabolic and ventilatory responses to cold in anesthetized cats.

Interactions between the control of thermogenesis and ventilation were studied during normoxia, hyperoxia, and ambient or CO hypoxia in adult anesthetized intact or carotid-denervated cats. Shivering, metabolic and ventilatory responses to cold stress were studied. In addition, the effects of transient pharmacological stimulation (NaCN) or inhibition (Dopamine) of arterial chemoreceptor activity were studied under different levels of oxygenation. In intact animals, cold exposure provoked increases in VO2 and ventilation which were directly proportional to the intensity of shivering. During ambient or CO hypoxia, VO2 was less than in normoxia for all values of shivering intensity, suggesting that a non-shivering thermogenesis component may also be inhibited by hypoxia. The decrease in VO2 was associated with a smaller decrease in ventilation in ambient than in CO hypoxia because of the presence of the chemoreflex drive during ambient hypoxia. Pharmacological changes in chemoreceptor activity induced transient and opposite changes in ventilation and shivering intensity, confirming their role in the control of thermogenesis. After carotid denervation, when the drug effects were inconsistent or absent, changes in levels of oxygenation were still followed by changes in shivering activity and associated changes in VO2 and ventilation. We conclude that control of thermogenesis and ventilation and their interaction may be mediated by chemoreceptors as well as by direct effects upon central, possibly diencephalic structures.

Animals↗

Cardiovascular responses to cold pressor test: a test for autonomic functions.

Circulatory dynamics during the cold pressor test, done by immersing the hand in water at 5 degrees C for one minute, were studied in 30 male healthy volunteers. All the subjects responded to the test with statistically significant increase in blood pressure (22.04%, p less than 0.001), heart rate (11.21%, p less than 0.001), galvanic skin resistance (36.17%, p less than 0.001) and decrease in forearm blood flow (40.85%, P less than 0.001). The measurement of cardiovascular responses following cold pressor test constitutes another test which can be used to test the efficiency of the autonomic nervous system in various autonomic neuropathies.

Adolescent↗

Contribution of adrenomedullin to homeostatic response to cold stress in rat model.

Acute stress known to stimulate sympathetic activity as well as the hypothalamo-pituitary-adrenal (HPA) axis, produces a significant increase in adrenomedullin (ADM) levels in the pituitary gland, plasma and adrenal glands, all of which are key components of HPA axis, suggesting a regulatory or protective role for ADM in countering HPA activation following a variety of physiological and psychological stressors. This study was conducted to assess a rat model for in depth investigation of biochemical mechanisms and consequences of cold stress. Four groups of Sprague-Dawley rats were observed for their serum total protein, glucose, trigliceride and cholesterol levels as well as their blood pressures after housing at room temperature, administration of ADM (1.0 nm/kg), exposing to cold stress (8 degrees C for 48 h) and exposing to ADM injection in addition to cold stress. The results suggest that application of ADM in addition to cold stress may act via receptors on different end-organs and causes altered metabolic regulation taking partial or total occupation of ADM receptors, stimulated in response to cold application induced physiologic ADM release before pharmacological ADM administration.

Journal Article↗

In vivo and in vitro studies on cold-induced airway response in normal and sensitized rabbits.

We measured the changes in lung resistance (RL) induced by cool inspired air under dry air conditions in anesthetized, paralyzed and artificially ventilated rabbits. We compared the airway response to cold air in non-sensitized (NS) animals with the response in rabbits sensitized (S) to bovine serum albumin. Using in vitro tracheal preparations from the same animals, we observed the effects of lowering the bath temperature on smooth muscle tension and also the response to acetylcholine (Ach). Dose-response curves to Ach were constructed and analyzed in terms of maximal contraction (delta Tmax) and pD2 coefficient (negative logarithm of the molar concentration of Ach producing 50% of maximum contraction). The magnitude of cold induced airway response tested in vivo was significantly greater in S (delta RL = +52% +/- 2) than in NS rabbits (+30% +/- 4; P less than 0.01). In vitro the decrease of temperature in the bathing medium induced a significant relaxation of tracheal spirals in both NS and S preparations (delta T = -2.42 +/- 0.34 g/mg wet tissue, -3.36 +/- 0.8 g/mg wet tissue, respectively). However, an adaptation of this response occurred after 8 min in NS rabbits whereas relaxation persisted in S rabbits. The tracheal contractile response to Ach was decreased by bath cooling in S ans NS animals (delta Tmax = 5.53 +/- 0.15 g/mg wet tissue and 5.03 +/- 0.27 g/mg wet tissue at 37 degrees C; 3.05 +/- 0.30 g/mg wet tissue and 1.93 +/- 0.35 g/mg wet tissue at 17 degrees C, respectively). Moreover, cooling also reduced the velocity of response. In all cases, S preparations displayed hyperresponsiveness to Ach and this was observed for maximal changes in tension as well as for pD2 values. Present observations show that cold induces different effects on airway smooth muscle with the production of a contractile response in in vivo preparations but relaxes isolated tracheal spirals. They also suggest that sensitization by foreign proteins may modify the intrinsic properties of tracheal smooth muscle.

Acetylcholine↗

Regulatory network of gene expression in the drought and cold stress responses.

Molecular and genomic studies have shown that several genes with various functions are induced by drought and cold stresses, and that various transcription factors are involved in the regulation of stress-inducible genes. The products of stress-inducible genes function not only in stress tolerance but also in stress response. Genetic studies have identified many factors that modify the regulation of stress responses. Recent progress has been made in analyzing the complex cascades of gene expression in drought and cold stress responses, especially in identifying specificity and crosstalk in stress signaling.

Acclimatization↗

Starvation suppresses sympathoadrenal medullary response to cold exposure in rats.

The effect of 2 days (55 h) of starvation on the functional state of the sympathetic nervous system (SNS) and adrenal medulla in male rats was evaluated in both normal (24 degrees C) and cold (4 degrees C) environments. Fasting (24 degrees C) significantly decreased NE turnover in heart and spleen, and the concentration of plasma epinephrine (E) and norepinephrine (NE). Cold exposure in the fed animals significantly increased NE turnover in the heart and plasma E, but had no effect on plasma NE or spleen NE turnover compared to normal (no stress) conditions. Cardiac NE turnover was 50% less in fasted cold-stressed animals than in fed cold-stressed animals. Plasma E remained at low levels. Plasma concentration of free fatty acids was significantly elevated in the fasted state in both warm and cold environments. These results suggest that 2 days of starvation in adult male rats suppresses the activity of the SNS and adrenal medulla and interferes with the normal adrenergic response to cold stress. Moreover, E appears not to be essential for mobilization of fat stores for energy metabolism in the fasted state in either warm or moderately cold environments.

Adrenal Medulla↗

Awareness of hypertension increases blood pressure and sympathetic responses to cold pressor test.

The present study was aimed at examining the effects of awareness of hypertension on blood pressure and sympathetic responses to the cold pressor test. Nineteen-year-old men with similarly elevated mean blood pressure at a medical screening, but without knowledge of this, were randomized into two groups. The first group (n = 16) was sent a letter saying that their pressure was too high, and the second (n = 13) was sent a neutral letter. Information increased mean blood pressure both after 15 min sitting, by an average of 11.5 mm Hg (P less than .01), and after 30 min supine rest, by an average of 4.5 mm Hg (P less than .05). Changes in heart rate (8.4 +/- 2.4 v 1.9 +/- 1.7 beats/min) and plasma epinephrine (0.11 +/- 0.04 v 0.01 +/- 0.03 nmol/L) during execution of a cold pressor test were significantly greater in the informed group (P less than .05). Plasma dopamine was lower in the informed group (P less than .05). Thus, psychological stress caused by the awareness of hypertension may increase blood pressure and sympathetic responses to a provocative maneuver. Ideally, studies on sympathetic function in essential hypertension should be undertaken on subjects unaware of their blood pressure status.

Adult↗

A follow up study of vibration induced white finger in compensation claimants.

AIMS: To follow up vibration induced white finger (VWF) in a selected group of 73 vibration exposed workers who claimed unsuccessfully for VWF compensation at a first examination. METHODS: The VWF claimants were sent to our unit by the National Insurance Institute. The basic compensatory criteria included a positive history of VWF and abnormal cold response of the digital arteries. Following the first unsuccessful examination, over a mean time period of 4.1 (range 1-11) years the National Insurance Institute requested a second examination for all 73 claimants and a third examination for 29. During the follow up period, all subjects continued to work with vibratory tools. RESULTS: There were 14 new cases who reported white finger during the follow up period. In the new VWF cases, finger blanching attacks became visible after about 3.5 years since the first examination. All incident cases of anamnestic VWF showed an abnormal cold response in the digital arteries and obtained compensation according to the basic compensatory criteria. In the entire sample of VWF claimants, there was a discrepancy between positive history of VWF symptoms at medical interview (55%) and abnormal cold provocation outcomes (19%). Digital arterial hyperresponsiveness to cold was associated with both VWF symptoms and the duration of vibration exposure since the first examination. Over the follow up period, a significant increase in the vasoconstrictor response to cold was observed in the vibration exposed workers with no symptoms of finger whiteness. Abnormal cold response was not associated with either age or smoking habit. CONCLUSIONS: Cold test measuring finger systolic blood pressure may be considered a useful laboratory method to confirm objectively VWF symptoms and to disclose abnormal cold induced vasoconstrictor response in vibration exposed workers with a negative history of VWF. Medical interview outcomes should be interpreted with caution in medicolegal situations involving VWF claimants.

Adult↗

Pulmonary responses during cold induced acute pain.

Cold induced acute pain is associated with many autonomic responses of the cardiovascular system, skin conductance and pupil size. However, there are few reports suggesting changes in pulmonary function. Hence present study reports preliminary data on this. Acute pain was induced in 30 non-smoker males, 30-50 yrs of age by immersing hand in cold water and their respiratory rate (RR), tidal volume (TV), inspiratory and expiratory reserve volumes (IRV, ERV) and respective capacities, vital capacity (VC), force vital capacity (FVC), FEV1%, peak flow and flow rates at 75%, 50% and 25% of expired volume (V75,50,25) were measured. Acute pain parameters like pain threshold, tolerance and sensitivity were also recorded. Besides these, heart rate, blood pressure (systolic and diastolic), skin temperature of forehead and opposite palm were also measured. Comparisons were made between values recorded before, during and after cold induced pain. An increase in RR, RV, IC, EC, FVC, FVC%, FEV1 was observed during cold induced pain reflecting an acute state of sympathetic dominance. Positive correlations between heart rate and respiratory rate, and other respiratory with pain parameters were seen during period of induction of acute pain. Hence the study indicates that alterations in pulmonary profile form a part of multidimensional responses observed during cold induced acute pain.

Acute Disease↗

Cell-Wall Changes and Cell Tension in Response to Cold Acclimation and Exogenous Abscisic Acid in Leaves and Cell Cultures.

Freeze-induced cell tensions were determined by cell water relations in leaves of broadleaf evergreen species and cell cultures of grapes (Vitis spp.) and apple (Malus domestica). Cell tensions increased in response to cold acclimation in leaves of broadleaf evergreen species during extracellular freezing, indicating a higher resistance to cell volume changes during freezing in cold-hardened leaves than in unhardened leaves. Unhardened leaves, typically, did not develop tension greater than 3.67 MPa, whereas cold-hardened leaves attained tensions up to 12 MPa. With further freezing there was a rapid decline and a loss of tension in unhardened leaves of all the broadleaf evergreen species studied. Also, similar results were observed in cold-hardened leaves of all of the species except in those of inkberry (Ilex glabra) and Euonymus fortunei, in which negative pressures persisted below -40[deg]C. Abscisic acid treatment of inkberry and Euonymus kiautschovica resulted in increases in freeze-induced tensions in leaves, suggesting that both cold acclimation and abscisic acid have similar effects on freezing behavior[mdash] specifically on the ability of cell walls to undergo deformation. Decreases in peak tensions were generally associated with lethal freezing injury and may suggest cavitation of cellular water. However, in suspension-cultured cells of grapes and apple, no cell tension was observed during freezing. Cold acclimation of these cells resulted in an increase in the cell-wall strength and a decrease in the limiting cell-wall pore size from 35 to 22 A in grape cells and from 29 to 22 A in apple cells.

Journal Article↗

Regulation of Sinorhizobium meliloti 1021 rrnA-reporter gene fusions in response to cold shock.

We previously reported that mutants of Sinorhizobium meliloti 1021 carrying luxAB insertions in each of the three 16S rRNA genes exhibited a dramatic (> or = 28-fold) increase in luminescence following a temperature downshift from 30 to 15 degrees C. These results raised the possibility that the rRNA operons (rrn) of S. meliloti were cold shock loci. In testing this possibility, we found that fusion of the S. meliloti 1021 rrnA promoter to two different reporter genes, luxAB and uidA, resulted in hybrid genes that were transiently upregulated (as measured by transcript accumulation) about four- to sixfold in response to a temperature downshift. These results are consistent with the hypothesis that the rrn promoters are transiently upregulated in response to cold shock. However, much of the apparent cold shock regulation of the initial luxAB insertions was due to an unexpected mechanism: an apparent temperature-dependent inhibition of translation. Specifically, the rrnA sequences from +1 to +172 (relative to the start of transcription) were found to greatly decrease the ability of S. meliloti to translate hybrid rrn-luxAB transcripts into active protein at 30 degrees C. This effect, however, was largely eliminated at 15 degrees C. Possible mechanisms for the apparent transient increase in rrnA promoter activity and temperature-dependent inhibition of translation are discussed.

Base Sequence↗

The role of the body mass: body surface ratio in thermo-regulatory responses to cold, hypoxia, and hypercapnia in new-born, adult, and aged guinea pigs.

The relationship between body weight (BW) and the changes in colonic temperature (deltaTc) was analyzed in newborn, adult, and old guinea pigs. No correlation could be demonstrated between BW and, deltaTc in response to cold with the exception of the 10 to 20 day-old group. In hypercapnia statistically significant or almost significant coefficient were obtained in three groups, showing--as expected--that the fall in Tc tended to decrease with increasing BW. In hypoxia a statistically significant coefficient was obtained in the young adult group, demonstrating that--contrary to expectation--the fall in Tc tended to be greater with increasing BW.

Aging↗