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Defect of cold-sensitive response in calmodulin mutants of Paramecium and the restoration by cyclic nucleotide.

Wild type and calmodulin mutants (cam) of Paramecium tetraurelia were examined for cold-sensitive responses. Among mutants tested, cam12 and cam13 mutants, which have substitutions in N-terminal lobe of calmodulin molecule, reduced both responses in the swimming and the membrane potential. Under voltage clamp conditions, the cooling stimulus to the wild type cell induced a transient inward current whose amplitude increased with the rate of temperature drop. The cam12 cell did not induce inward currents in response to cooling with a rate slower than -0.4 degree C/s. The reduced current response of cam12 mutant was restored by an external application of a phosphodiesterase inhibitor, theophylline. Also, an intracellular injection of hydrolysis-resistant cyclic nucleotides, either 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5'-cyclic monophosphate (8-Br-cGMP), restored the current response. Such restoration was accompanied by shifts of the resting potential to hyperpolarized levels and by an increase in the membrane conductance. The results suggest the possibility that calmodulin and cyclic nucleotide regulate K+ channels responsive to the cooling stimulus.

Animals↗

Accumulation of dehydrin-like proteins in the mitochondria of cereals in response to cold, freezing, drought and ABA treatment.

BACKGROUND: Dehydrins are known as Group II late embryogenesis abundant proteins. Their high hydrophilicity and thermostability suggest that they may be structure stabilizers with detergent and chaperone-like properties. They are localised in the nucleus, cytoplasm, and plasma membrane. We have recently found putative dehydrins in the mitochondria of some cereals in response to cold. It is not known whether dehydrin-like proteins accumulate in plant mitochondria in response to stimuli other than cold stress. RESULTS: We have found five putative dehydrins in the mitochondria of winter wheat, rye and maize seedlings. Two of these polypeptides had the same molecular masses in all three species (63 and 52 kD) and were thermostable. Drought, freezing, cold, and exogenous ABA treatment led to higher accumulation of dehydrin-like protein (dlp) 63 kD in the rye and wheat mitochondria. Protein 52 kD was induced by cold adaptation and ABA. Some accumulation of these proteins in the maize mitochondria was found after cold exposition only. The other three proteins appeared to be heat-sensitive and were either slightly induced or not induced at all by all treatments used. CONCLUSIONS: We have found that, not only cold, but also drought, freezing and exogenous ABA treatment result in accumulation of the thermostable dehydrins in plant mitochondria. Most cryotolerant species such as wheat and rye accumulate more heat-stable dehydrins than cryosensitive species such as maize. It has been supposed that their function is to stabilize proteins in the membrane or in the matrix. Heat-sensitive putative dehydrins probably are not involved in the stress reaction and adaptation of plants.

Abscisic Acid↗

Afferent new fiber activity responding to temperature changes of scrotal skin of the rat.

The discharge patterns of single afferent fibers from rat pudendal nerve were studied as a function in temperature of the scrotal skin, an area known to function in temperature regulation. In a number of respects the population of temperature-sensitive afferents here differ from most previously described; 75% of temperature-sensitive afferents were also sensitive to mechanical stimulation. Of the 25% nonmechanosensitive units, half showed dynamic and static responses to cooling, while most of the remaining fibers gave only static discharges to warming. The most frequent thermal reaction of the mechanosensitive units was a dynamic-static cold response or a pure static warm response. However, fibers were also present with only dynamic or only static cold responses. Of the bimodal units, 20% had a dynamic cold response, but showed a minimal static discharge at intermediate temperatures (about 35 degrees C) and an increased discharge on both warming and cooling from that temperature. One unit had static and dynamic warm responses. Whereas a bursting discharge in the cold has previously been considered to be a distinguishing characteristic of specific cold receptors, in the pudendal afferents a bursting discharge on cooling or at low temperatures is common both in mechanosensitive and specific cold fibers. This observation and the identical discharge patterns and mechanisms underlying the thermosensitivity argue for the view that the mechanosensitive afferents participate in thermal sensation and/or regulation along with the specific temperature receptors. Hellon and Misra (7) have concluded that there is processing of thermal information from the scrotal skin at the level of the first synapse in the cord. However, in this study, we have found peripheral afferents which have most of the discharge properties that led Hellon and Misra to conclude that processing had occurred. The unusual characteristics of thermosensitive afferents of the pudendal nerve suggest that there is probably organ specificity of neuronal discharge properties.

Action Potentials↗

An investigation into the changed physiological state of Vibrio bacteria as a survival mechanism in response to cold temperatures and studies on their sensitivity to heating and freezing.

AIMS: To induce pathogenic Vibrio bacteria into a changed physiological state, in response to cold temperatures in sea water, and assess their sensitivity to heating and freezing, as compared with normal cells. METHODS AND RESULTS: Cells of exponential phase Vibrio vulnificus, V. cholerae and V. parahaemolyticus were washed and inoculated into flasks of sea water, which were stored at 20 and 4 degrees C. Cells stored at 20 degrees C could be recovered after 60 d on non-selective agar (heart infusion agar; HIA) and on the selective agar (thiosulphate citrate bile salts agar) which is used in most Vibrio detection methodology. At 4 degrees C cells became non-culturable on both agars over time. The non-culturable cells appeared to be metabolically active and maintained their membrane integrity, whilst undergoing a change in morphology from rod-shaped to coccoid cells. Resuscitation was possible, in some cases, by an upshift in temperature before plating and the addition of catalase to HIA plates was found to increase recovery. Studies were carried out to assess the sensitivity of the non-culturable cells to heating and freezing compared with the normal cells. Vibrio organisms, whether culturable or in the non-culturable form, were not inactivated by freezing to -20 degrees C. Heating studies showed that V. parahaemolyticus was very heat resistant at low temperatures. However, a pasteurization regime of 2 min at 70 degrees C was found to be effective against all three strains. Experiments showed that the non-culturable cells of all three strains were similar in their heat resistance or, in some cases, were more heat sensitive than cells in the normal form. CONCLUSIONS: Cells in the changed physiological form would not be detected in fish or seafood products by the current Vibrio detection methods. Freezing had no effect in reducing cell numbers. Vibrio parahaemolyticus was very heat resistant in the low temperature pasteurization studies. The higher pasteurization regime of 70 degrees C for 2 min was effective against all three pathogens. Non-culturable cells had similar heat sensitivity or were more heat sensitive than cells in the normal state. SIGNIFICANCE OF IMPACT OF THE STUDY: The study has highlighted a need for the development of better Vibrio detection methods. The low temperature pasteurization of oysters, which has been recommended in the USA, would not be adequate against the strain of V. parahaemolyticus used in this study. Heating regimes which were found to control cells in the normal form will also be effective for the control of the cells with changed physiology.

Agar↗

Consistency of hemodynamic responses to cold stress in adolescents.

Laboratory research on hypertension often is performed with cold stress to elicit vasoconstriction and increases in blood pressure. Several studies have shown that cardiovascular responses to the cold pressor test predict the development of hypertension. We extended this research by comparing cardiovascular responses to a traditional forehead cold pressor test and a naturalistic whole-body cold exposure. We evaluated blood pressure and impedance cardiographic measures of cardiac output and total peripheral resistance in healthy black (n=69) and white (n=47) adolescents (mean age, 14.7 years) during forehead cold pressor (3 degrees C to 4 degrees C) and passive whole-body exposure to a cold chamber (8 degrees C to 10 degrees C). Both tasks elicited increases in vascular resistance and blood pressure, but forehead cold elicited an increase in cardiac output, whereas whole-body cold elicited a decrease in cardiac output (P<0.05). Consistent with previous research, there was a tendency toward greater vasoconstrictive reactivity to cold stress in blacks than in whites, particularly during whole-body cold exposure (P<0.05). Cardiovascular reactivity correlated significantly between tasks, but substantial intertask consistency occurred only for cardiac and vascular reactivity in male subjects (r>0.30) but not in female subjects (r<0.15). These gender differences might reflect diminished adrenergic receptor function in female subjects. We conclude that whole-body cold exposure offers a viable, relatively naturalistic alternative to traditional cold pressor tests for the assessment of cardiovascular reactivity.

Adolescent↗

Coronary vasoconstrictor response to cold pressor test in variant angina: lack of relation to intracoronary thromboxane concentrations.

To test the hypothesis that intracoronary concentrations of thromboxane (Tx)A2 could influence the response to cold pressor test (CPT) in variant angina, great cardiac vein blood flow (by thermodilution) and the concentration of TxB2 (the stable metabolite of TxA2) in the great cardiac vein and aorta were measured under control conditions and during CPT in 14 patients with angina at rest associated with transient ST-segment elevation in the anterior leads. In seven patients pretreated with aspirin (intravenous administration of 3.6 mg/kg lysine salt of acetylsalicylic acid, corresponding to 2 mg/kg aspirin), TxB2 baseline concentrations were lower in both the great cardiac vein (47 +/- 19 vs 176 +/- 88 pg/ml; p less than 0.005) and the aorta (45 +/- 16 vs 109 +/- 56 pg/ml, p less than 0.02) than in seven patients who were not taking cyclooxygenase inhibitors. In the two groups, great cardiac vein flow and anterior region coronary resistance were similar under control conditions. During CPT anterior region coronary resistance increased in patients pretreated with aspirin (from 1.97 +/- 0.99 to 2.22 +/- 1.11 mm Hg/ml/min; p less than 0.02) and in patients without aspirin pretreatment (from 1.94 +/- 0.43 to 2.06 +/- 0.34 mm Hg/ml/min; p less than 0.05), and the difference between the two groups was not statistically significant. Therefore the vasoconstrictor response of coronary vessels to CPT in variant angina is not influenced by the intracoronary TxB2 concentrations and is not modified by aspirin pretreatment.

Adult↗

Roles of the CBF2 and ZAT12 transcription factors in configuring the low temperature transcriptome of Arabidopsis.

Summary The CBF cold response pathway has a prominent role in cold acclimation. The pathway includes action of three transcription factors, CBF1, 2 and 3 (also known as DREB1b, c and a, respectively), that are rapidly induced in response to low temperature followed by expression of the CBF-targeted genes (the CBF regulon) that act in concert to increase plant-freezing tolerance. The results of transcriptome profiling and mutagenesis experiments, however, indicate that additional cold response pathways exist and may have important roles in life at low temperature. To further understand the roles that the CBF proteins play in configuring the low temperature transcriptome and to identify additional transcription factors with roles in cold acclimation, we used the Affymetrix GeneChip containing probe sets for approximately 24,000 Arabidopsis genes to define a core set of cold-responsive genes and to determine which genes were targets of CBF2 and 6 other transcription factors that appeared to be coordinately regulated with CBF2. A total of 514 genes were placed in the core set of cold-responsive genes, 302 of which were upregulated and 212 downregulated. Hierarchical clustering and bioinformatic analysis indicated that the 514 cold-responsive transcripts could be assigned to one of seven distinct expression classes and identified multiple potential novel cis-acting cold-regulatory elements. Eighty-five cold-induced genes and eight cold-repressed genes were assigned to the CBF2 regulon. An additional nine cold-induced genes and 15 cold-repressed genes were assigned to a regulon controlled by ZAT12. Of the 25 core cold-induced genes that were most highly upregulated (induced over 15-fold), 19 genes (84%) were induced by CBF2 and another two genes (8%) were regulated by both CBF2 and ZAT12. Thus, the large majority (92%) of the most highly induced genes belong to the CBF and ZAT12 regulons. Constitutive expression of ZAT12 in Arabidopsis caused a small, but reproducible, increase in freezing tolerance, indicating a role for the ZAT12 regulon in cold acclimation. In addition, ZAT12 downregulated the expression of the CBF genes indicating a role for ZAT12 in a negative regulatory circuit that dampens expression of the CBF cold response pathway.

Acclimatization↗

Clinical defense response to cold and noise in preterm neonates after intrauterine conditions associated with chronic stress.

Threatening stimuli may trigger abnormal reaction patterns in animals and infants. We investigated whether chronic intrauterine stress influenced these reactions. The autonomic defense response to cold and noise in 21 preterm newborns who had suffered from chronic intrauterine stress, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR-group) was compared with the response in 30 preterm newborns without such condition (C-group). An ice cube was applied to the forehead and a 90 dB bleeptone was presented to the ears. After the cold test the heart rate, systolic, diastolic, and mean blood pressure increased in both groups, but to a lesser extent in the STR-group: the heart rate increased more at 2 minutes in the C-group (p = 0.009), and the systolic blood pressure was higher in the C-group at 30 seconds (p = 0.007). The respiratory rate decreased in both groups. After the auditory stimulus, no significant difference in response between the two groups was seen for any of the parameters. The number of arousals between the two groups was similar for both tests; they uniformly resulted in increased heart and respiratory rates. The classic passive defense response was not observed in either group of preterm newborns. The observed reaction could be defined as a combination of a sympathetic, active fight-or-flight reaction and a parasympathetic passive freezing, or paralysis, reaction. The latter was less pronounced in the C-group. This may point to a change in the maturation of the autonomic nervous system after chronic intrauterine stress. It is speculated that this could make these infants more vulnerable in stressful situations.

Adult↗

Site-dependent action of intracerebroventricular 5-hydroxytryptamine on the cold-stimulated thyrotropin secretion in male rats.

The effects of central 5-hydroxytryptamine (5-HT) infusions on the cold-stimulated thyrotropin (TSH) levels were studied in male rats. Stainless-steel cannulas were implanted stereotaxically into the anterior or the posterior third ventricle or just lateral to the hypothalamic paraventricular nuclei bilaterally 7 days before experiments. Infusion of 5-HT (4.5 and 9 micrograms/rat) into the posterior third ventricle attenuated significantly the cold-stimulated TSH levels. Inversely, infusion of 5-HT (9 micrograms/rat) into the anterior third ventricle augmented significantly the TSH cold response. Bilateral 5-HT infusions into the vicinity of the hypothalamic paraventricular nuclei did not affect the TSH cold response. Serum prolactin levels increased significantly after 5-HT administration into the anterior and the posterior third ventricle, but no consistent effect on growth hormone (GH) levels could be detected. Infusion of 5-HT into the anterior and the posterior third ventricle decreased body temperature irrespective of the observed hormonal response to 5-HT. The results are in favor of a dual and possibly site-dependent role for 5-HT in the regulation of the cold-stimulated TSH secretion in the rat. The opposite effects of 5-HT on the TSH cold response may result from the predominant inhibition of either the thyrotropin-releasing hormone or the somatostatin-secreting cell groups.

Animals↗

Effects of prostacyclin on coronary hemodynamics at rest and in response to cold pressor testing in patients with angina pectoris.

To assess the effect of prostacyclin on the diseased coronary circulation basally and, in particular, on the coronary responses to the cold pressor test, a small dose of 4 ng/kg/min and a large dose of 8 to 10 ng/kg/min was infused in 11 patients with stable angina pectoris. Coronary blood flow was measured by coronary sinus thermodilution technique. The mean blood pressure decreased from 97 +/- 5 to 89 +/- 5 mm Hg during the low-dose infusion (p less than 0.005) and to 81 +/- 5 mm Hg during the high-dose infusion (p less than 0.001); the heart rate increased from 65 +/- 4 to 69 +/- 4 beats/min during the low-dose infusion (p less than 0.05) and to 78 +/- 5 beats/min during the high-dose infusion (p less than 0.001). Systemic vascular resistance decreased by 11 +/- 4% with small doses (p less than 0.05) and by 38 +/- 4% with large doses (p less than 0.001) of prostacyclin, and coronary vascular resistance decreased by 16 +/- 7% (p less than 0.05) with the small dose and by 29 +/- 6% (p less than 0.001) with the large dose of prostacyclin. Seven of 11 patients showed a baseline vasoconstrictor response to the cold pressor test (increase in coronary vascular resistance of 11 +/- 2%). This increase in coronary vascular resistance was not altered by either the small or the large dose of prostacyclin. Thus, prostacyclin causes marked coronary and systemic vasodilation, with no evidence of selective enhancement of the sensitivity of the diseased coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Effect of eprosartan on the sympathetic response to cold pressor test in healthy volunteers.

The aim of this study was to evaluate the effect of short-term administration of the AT1 angiotensin II receptor antagonist, eprosartan, on the sympathetic response to cold pressor test (CPT) in normotensive healthy volunteers. Sixty-nine healthy volunteers were included in this double-blind placebo-controlled study. Blood pressure and heart rate were determined before and 175 min after oral administration of placebo, losartan (50 mg) or eprosartan (600 mg). Immediately, the subjects underwent CPT and then the same hemodynamic variables were measured. CPT increased arterial blood pressure (systolic, diastolic and mean) and HR in placebo-treated group. Pretreatment with a single dose of losartan or eprosartan blunted CPT-induced pressor response, but not the rise in heart rate. Our results demonstrate that endogenous angiotensin II, through stimulation of AT1 receptor, supports sympathetic mediated stress-response in humans.

Acrylates↗

Cold shock response in sporulating Bacillus subtilis and its effect on spore heat resistance.

Cold shock and ethanol and puromycin stress responses in sporulating Bacillus subtilis cells have been investigated. We show that a total of 13 proteins are strongly induced after a short cold shock treatment of sporulating cells. The cold shock pretreatment affected the heat resistance of the spores formed subsequently, with spores heat killed at 85 or 90 degrees C being more heat resistant than the control spores while they were more heat sensitive than controls that were heat treated at 95 or 100 degrees C. However, B. subtilis spores with mutations in the main cold shock proteins, CspB, -C, and -D, did not display decreased heat resistance compared to controls, indicating that these proteins are not directly responsible for the increased heat resistance of the spores. The disappearance of the stress proteins later in sporulation suggests that they cannot be involved in repairing heat damage during spore germination and outgrowth but must alter spore structure in a way which increases or decreases heat resistance. Since heat, ethanol, and puromycin stress produce similar proteins and similar changes in spore heat resistance while cold shock is different in both respects, these alterations appear to be very specific.

Bacillus subtilis↗

The cold-shock response in cultured mammalian cells: harnessing the response for the improvement of recombinant protein production.

There are a growing number of reports on the sub-physiological temperature culturing (<37 degrees C) of mammalian cells for increased recombinant protein yield, although the effect is variable between cell lines, expression systems, and the product of interest. What is becoming clear is that exposing mammalian cells to sub-physiological temperatures invokes a coordinated cellular response involving modulation of the cell cycle, metabolism, transcription, translation, and the cell cytoskeleton. Opportunities currently exist for further enhancement of the cold-shock effect on recombinant protein production in mammalian cells through advancements in our understanding of the mechanisms involved in the cold-shock response.

Animals↗

Bacterial cold shock responses.

As a measure for molecular motion, temperature is one of the most important environmental factors for life as it directly influences structural and hence functional properties of cellular components. After a sudden increase in ambient temperature, which is termed heat shock, bacteria respond by expressing a specific set of genes whose protein products are designed to mainly cope with heat-induced alterations of protein conformation. This heat shock response comprises the expression of protein chaperones and proteases, and is under central control of an alternative sigma factor (sigma 32) which acts as a master regulator that specifically directs RNA polymerase to transcribe from the heat shock promotors. In a similar manner, bacteria express a well-defined set of proteins after a rapid decrease in temperature, which is termed cold shock. This protein set, however, is different from that expressed under heat shock conditions and predominantly comprises proteins such as helicases, nucleases, and ribosome-associated components that directly or indirectly interact with the biological information molecules DNA and RNA. Interestingly, in contrast to the heat shock response, to date no cold-specific sigma factor has been identified. Rather, it appears that the cold shock response is organized as a complex stimulon in which post-transcriptional events play an important role. In this review, we present a summary of research results that have been acquired in recent years by examinations of bacterial cold shock responses. Important processes such as cold signal perception, membrane adaptation, and the modification of the translation apparatus are discussed together with many other cold-relevant aspects of bacterial physiology and first attempts are made to dissect the cold shock stimulon into less complex regulatory subunits. Special emphasis is placed on findings concerning the nucleic acid-binding cold shock proteins which play a fundamental role not only during cold shock adaptation but also under optimal growth conditions.

Adaptation, Physiological↗

Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep.

Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Base Sequence↗

Preliminary study on the assessment of peripheral vascular response to cold provocation in workers exposed to hand-arm vibration using laser Doppler perfusion imager.

Measurements of changes in finger skin blood flow with laser Doppler perfusion imaging (LDPI) in response to cold provocation test (10 degrees C, 10 min) were performed in 12 men suffering from vibration induced white finger (VWF) and 13 exposed controls. The mean perfusion values in both groups reduced markedly as a result of immersion of the hand in cold water. In the controls, however, the mean value increased gradually until the end of the cold provocation, while that in the VWF subjects remained at the lowest level. After removal of the hand from the cold water, the skin blood perfusion in the controls recovered rapidly and nearly reached the baseline value. In the VWF subjects, it had a slight increase immediately following the cold immersion but no tendency to rise as the time span increased. Analysis of covariance controlling for possible confounders revealed that the VWF subjects had significantly lower perfusion values compared to the controls in the last several minutes of the cold provocation and the following recovery. These findings suggest that the LDPI technique enables visualizing and quantifying the peripheral vascular effects of cold water immersion on the finger skin blood perfusion and thus has the potential of providing more detailed and a&curate information that may help detect the peripheral circulatory impairment in the fingers of vibration-exposed workers.

Arm↗

Clonidine decreases vasoconstriction and shivering thresholds, without affecting the sweating threshold.

PURPOSE: This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds. METHODS: Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control), 3, 6 or 9 micrograms.kg-1. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37 degrees C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g.m-2.h-1). The water was then cooled gradually until thresholds for vasoconstriction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation in metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33 degrees C. RESULTS: High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1.16 +/- 0.30 degrees C and for shivering by 1.63 +/- 0.23 degrees C (P < 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivering thresholds decreasing by 0.13 +/- 0.05 and 0.19 +/- 0.09 degree C.microgram-1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstriction thresholds increased from control (0.19 +/- 0.48 degree C) to high dose clonidine (1.31 +/- 0.54 degrees C). CONCLUSION: The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.

Adrenergic alpha-Agonists↗