Cooling-induced Contraction Research Articles

Converse two-way shape memory effect through a dynamic covalent network design

A unique thermally driven two-way shape memory polymer is reported through a dynamic covalent network design. Its actuation direction relative to the programming force is reflected as cooling-induced contraction and heating-induced elongation.

Hypothermia induces opposite response in vascular and non-vascular smooth muscles.

The mechanism of cooling-induced response of smooth muscles remains little understood despite the increasing importance given to it in recent years. The aim of this study was to examine the possibility of releasing a relaxant or a contractile substance during cooling from vascular and non-vascular smooth muscles. Assessing the effect of cooling for two different smooth muscles together, vascular (aorta or carotid) which induced relaxation, and non-vascular (jejunum or bladder) which induced contraction. Hanging a pair of smooth muscle strips from different body organs in the same organ bath filled with Krebs solution, each strip was connected to its own transducer and recorder and stepwise cooling was applied. Recordings of isometric tension using organ-bath techniques. Step-wise cooling (37°C-4°C) of aorta and carotid smooth muscle preparations induced reproducible graded relaxation while jejunum and bladder preparations induced reproducible graded tonic contractions, inversely proportional to temperature. The responses of all the smooth muscle preparations were the same magnitude either alone or as a pair in the organ bath. Cooling abolished rhythmic smooth muscle activity of jejunum and bladder. Cooling-induced contraction was reduced by incubation in Ca2+-free solution. The effect of cooling either relaxation or contraction was not enhanced or attenuated by the presence of the two different smooth muscles with opposite response in the same organ bath, proving the absence of a relaxant or a contractile substance released during cooling. Cooling of aorta and carotid artery induced relaxation while jejunum and bladder induced contraction. The response to cooling is inversely proportional to the temperature. There was neither a relaxant nor a contractile substance released from vascular or non-vascular smooth muscles during cooling. Our study suggested that the effect of cooling is through a thermal receptor with two subtype one in the vascular smooth muscle (deep blood vessels) which induces relaxation, and the second in non-vascular smooth muscles (non-vascular organs) that induces contraction and the responses depend on extracellular calcium.

Disclosing the temperature of columnar jointing in lavas

Columnar joints form by cracking during cooling-induced contraction of lava, allowing hydrothermal fluid circulation. A lack of direct observations of their formation has led to ambiguity about the temperature window of jointing and its impact on fluid flow. Here we develop a novel thermo-mechanical experiment to disclose the temperature of columnar jointing in lavas. Using basalts from Eyjafjallajökull volcano (Iceland) we show that contraction during cooling induces stress build-up below the solidus temperature (980 °C), resulting in localised macroscopic failure between 890 and 840 °C. This temperature window for incipient columnar jointing is supported by modelling informed by mechanical testing and thermal expansivity measurements. We demonstrate that columnar jointing takes place well within the solid state of volcanic rocks, and is followed by a nonlinear increase in system permeability of <9 orders of magnitude during cooling. Columnar jointing may promote advective cooling in magmatic-hydrothermal environments and fluid loss during geothermal drilling and thermal stimulation.

Effect of pregnancy on cooling tone and rhythmic contractions of the rat urinary bladder.

Pregnancy is a physiological alteration that can affect urinary bladder. Cooling of urinary bladder smooth muscle is known as a potent stimulus to micturition due to an increase in muscle tone. The current study investigates the effects of pregnancy on cooling tone and on the rhythmic contractions of the urinary bladder. Twenty-four rats were used in this study as control group (non-pregnant) and pregnant group (18-20-day pregnancy). Isolated rat urinary muscle strips were suspended in organ baths containing Krebs' solution for isometric tension recording. Cooling from 37 to 5°C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. Cooling also increased the rhythmic activity (amplitude and frequency) at 30 and 25°C, then decreased at 20°C, and abolished at 15-5°C. These responses were more pronounced in pregnant group than in control group. Rhythmic contractions were abolished in calcium-free, EGTA (1mM)-containing Krebs' solution and in the presence of nifedipine, while they were not affected by CPA or TTX in both groups. Our investigation showed that the influx of extracellular calcium is important in inducing the rhythmic contractions. Pregnancy increases cooling-induced contraction in pregnant rat urinary preparations and its rhythmic contractions including amplitude and frequency than non-pregnant rat. Rhythmic contractions are myogenic in nature and highly extracellular calcium dependent. They may play a crucial role in urinary bladder overactivity and incontinence during pregnancy.

Reversing cooling flows with AGN jets: shock waves, rarefaction waves and trailing outflows

The cooling flow problem is one of the central problems in galaxy clusters, and active galactic nucleus (AGN) feedback is considered to play a key role in offsetting cooling. However, how AGN jets heat and suppress cooling flows remains highly debated. Using an idealized simulation of a cool-core cluster, we study the development of central cooling catastrophe and how a subsequent powerful AGN jet event averts cooling flows, with a focus on complex gasdynamical processes involved. We find that the jet drives a bow shock, which reverses cooling inflows and overheats inner cool core regions. The shocked gas moves outward in a rarefaction wave, which rarefies the dense core and adiabatically transports a significant fraction of heated energy to outer regions. As the rarefaction wave propagates away, inflows resume in the cluster core, but a trailing outflow is uplifted by the AGN bubble, preventing gas accumulation and catastrophic cooling in central regions. Inflows and trailing outflows constitute meridional circulations in the cluster core. At later times, trailing outflows fall back to the cluster centre, triggering central cooling catastrophe and potentially a new generation of AGN feedback. We thus envisage a picture of cool cluster cores going through cycles of cooling-induced contraction and AGN-induced expansion. This picture naturally predicts an anti-correlation between the gas fraction (or X-ray luminosity) of cool cores and the central gas entropy, which may be tested by X-ray observations.

198 - Does TRP channel play a role in cooling-induced contraction of human detrusor smooth muscle?

198 - Does TRP channel play a role in cooling-induced contraction of human detrusor smooth muscle?

Volume changes of an unsaturated clay during heating and cooling

Thermally induced soil volume changes can have significant influence on many geotechnical structures. So far, research on thermal volume changes of unsaturated soil is very limited, particularly at temperatures lower than typical room temperature (23°C). The principal objective of this study is to investigate the volumetric behaviour of normally consolidated intact and recompacted low-plasticity clay specimens (loess soil) over a wide thermal cycle ranging from 5 to 53°C using a modified double-cell triaxial apparatus. It is found that contractive volumetric strain increases as the temperature increases. During the cooling process, soil volume keeps contracting until the temperature decreases to 5°C. Different from previous studies in the literature on saturated remoulded illite and natural silty clay, a plastic contraction at a much higher rate is observed from 13 to 5°C for both recompacted and intact loess specimens. The plastic volume changes during cooling are probably because cooling-induced contraction of soil particles leads to particle rearrangements in loess. Moreover, the cooling-induced plastic volume change, which only occurs when the cooling temperature is less than a critical value (13°C for the test conditions considered in this study), cannot be captured by the existing thermo-mechanical models, which predict elastic contraction during cooling. A new yield surface (temperature decrease) is proposed to simulate the observed elastoplastic behaviour during cooling.

Evaluation of different anti-asthmatic drugs on cooling-induced bronchoconstriction

Inhalation of cold air is a well-recognized cause of bronchoconstriction in asthmatics. Sudden changes in weather temperature outdoors and indoors due to the extensive use of air conditioning in Kuwait is an important existing problem. The aim of this study was to determine the most effective anti-asthmatic drugs for preventing or reversing cooling-induced contraction (CIC). We recorded isometric tension from tracheal strips, and bronchiolar rings were prepared from male Merino sheep in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents. Disodium cromoglycate (DSG), methyl prednisolone, atropine, aminophylline, isoprenaline and adrenaline were examined in two cases. The first was before cooling and the second was after cooling induced the maximum bronchoconstriction. Cooling to 20°C induced a rapid and reproducible contraction in ovine tracheal and bronchial preparations. On readjustment to 37°C, the tone returned rapidly to basal level. DSG, methyl prednisolone and atropine did not prevent or reverse the CIC. Aminophylline prevented CIC by 70%. It inhibited the peak of cooling response by 70%. β-agonists (isoprenaline and adrenaline) abolished the CIC, and they also rapidly and totally reversed the cooling effect when added at the peak of bronchoconstriction. These results proved that β-agonists are the drugs of choice in preventing the bronchoconstriction before exposure to cold environment and also completely reversing the bronchoconstriction induced after cooling exposure.

Cooling-induced contraction in ileal longitudinal smooth muscle of guinea-pig.

The ileal longitudinal smooth muscle developed a transient contraction on cooling from 37 degrees C to 1 degree C in normal Ca2+ (2.5 mM) medium. The transient contraction was not inhibited by pretreatment with the Ca2+ antagonist, D-600 (1 X 10(-6)M). The contractions were sustained by cooling to 1 degree C in the presence of added Ca2+ greater than 10 mM. After the pretreatment with D-600, when the muscle incubated in normal medium with added 20 mM Ca2+ had been cooled to 1 degree C, a phasic response was only seen. However, D-600 did not inhibit the sustained contraction at 1 degree C after incubation in the presence of added 20 mM Ca2+. It is suggested that the transient and sustained contraction at 1 degree C is maintained by Ca2+ release from a cellular site, probably the cell membrane and it requires more calcium for the sustained tension.

Effect of vanadate on cooling-induced tension changes in K-depolarized smooth muscles from guinea-pigs

Sodium vanadate reversed cooling-induced relaxation of K-depolarized taenia coli of guinea-pigs but failed to reverse it in the portal vein and uterus. It potentiated cooling-induced contraction of K-depolarized vas deferens and ureter. These effects were not mediated by the inhibition of Na,K-ATPase, but by the inhibition of the Ca-pump.

Effect of acute cold exposure on lung perfusion and tracheal smooth muscle contraction in rabbit

Acute exposure to cold temperature can affect the respiratory system of those exposed to extreme weather and induces asthma in asthmatic patients. However, the effect on lung perfusion and the pulmonary circulation was not addressed in any previous study. The present study investigates the effects of acute cold exposure on tracheal smooth muscle and lung perfusion. New Zealand White rabbits were used in these experiments. For in vitro experiments, isolated tracheal segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue response to cooling from 37 to 4°C was examined. For in vivo experiments, the rabbits were kept in a cold room (4°C) for 1h. Lung perfusion scintigraphy was performed at the end of this period. Each rabbit was injected with 74MBq (2mCi) technetium-99m macroaggregated ((99m)Tc MAA). Perfusion studies were done by using Gamma camera equipped with a low-energy, high-resolution, parallel-hole collimator interfaced with a computer. Static images were acquired 5min after administration of the radiotracer. Cooling induced a rapid and reproducible contraction in the tracheal smooth muscle. Rabbits exposed to cold temperature had lesser lung perfusion than controls using radionuclide perfusion study. Our results highlight the response of tracheal muscle and pulmonary circulation to cold exposure. These results indicate that cooling induced contraction of the trachea and decreased pulmonary circulation and lung perfusion. This summation of acute cooling for tracheal smooth muscle and pulmonary circulation seems to be the reason for the severe cooling-induced contraction.

Effect of Diabetes on Cooling-induced Detrusor Muscle Contraction: Mediation Via Rho-kinase Activation

To investigate the possible involvement of Rho-kinase in cooling-induced contraction of the detrusor muscle. The etiology of diabetic cystopathy is not clear. It may be due to various changes in bladder innervation and/or detrusor muscle dysfunction. Because cooling of urinary bladder smooth muscle normally is a potent stimulus to micturition due to increase in muscle tone, we studied the effects of cooling on normal and diabetic bladder specimens. Urinary detrusor muscle strips isolated from rats were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to stepwise cooling were examined from normal and 12-week streptozocin-induced diabetic rats. We examined the effects of calcium-free, ethylene glycol bis (beta-aminoethylether)-N,N,N,N,-tetraacetic acid (1 mm)-containing Krebs solution, and the Rho-kinase inhibitor Y-27632 on the cooling responses. Stepwise cooling from 37 degrees C to 5 degrees C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. This response was more pronounced in diabetic specimens. Cooling-induced contractions were significantly inhibited in calcium-free solutions in both control and diabetic bladders. Our investigation showed that the influx of extracellular calcium is important in inducing the cooling response. The Rho-kinase inhibitor Y-27632 (1 microm) inhibited cooling (20 degrees C)-induced contraction. It reduced the response by 52.1% +/- 10.0% in control and by 70.0% +/- 12.0% in diabetic rats. Cooling-induced contractions in control and diabetic detrusor muscle preparations are highly calcium dependant. It also involves activation of Rho-kinase, which might be upregulated in the diabetic detrusor muscle. These results may help in the management of diabetes-induced incontinence due to involuntary detrusor muscle activity.

Verapamil Induces Calcium Influx in the Trachea

Verapamil, a Ca2+entry blocker, can induce bronchorelaxation and bronchoconstriction. The mechanism of verapamil-induced bronchoconstriction is poorly understood. The present study determines the direct effect of verapamil on smooth muscle of isolated ovine airways and analyzes the mechanisms involved. Isolated tracheal strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to verapamil as assessed by basal tone were examined in the presence or absence of epithelium. The effects of verapamil on carbachol and cooling-induced contraction were also recorded. Measurement of unidirectional fluxes was carried out using 45Ca2+in the absence or presence of verapamil. Verapamil induced contractions of basal tracheal smooth muscle that were proportional to its concentrations. Removal of epithelium did not affect the verapamil contractile effect. Verapamil-induced contractions were abolished in Ca2+-free Krebs solution containing 2 mM EGTA. Verapamil increased the 45Ca2+influx into the tracheal smooth muscle. It caused relaxation of the muscle tone induced by carbachol or KCl, but it potentiated the effect of cooling-induced contraction. Verapamil induced Ca2+influx that may lead to bronchoconstriction. These results proved that verapamil may worsen bronchoconstriction; therefore verapamil should be used with caution in asthmatic individuals.

Cooling‐induced contraction of the rat gastric fundus: Mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho‐kinase activation

1. Cooling has been shown to induce contractions of several smooth muscles in vitro. However, the mechanism involved in the response is not yet known. In the present study, we investigated the possible involvement of transient receptor potential (TRP) cation channel TRPM8 receptors and the Rho-kinase pathway in cooling-induced contraction of the rat fundus. 2. Cooling-induced contractions were inversely proportional to temperature. Contractions were significantly reduced (by 65.6 +/- 2.4%; P < 0.05) in a Ca2+-free (1 mmol/L EGTA) medium, but were not significantly inhibited by nifedipine (10(-6) mol/L). 3. Capsazepine (3 x 10(-6) and 3 x 10(-5) mol/L), a TRPM8 receptor antagonist, inhibited cooling-induced contraction of the rat gastric fundus. 4. The Rho-kinase inhibitor Y-27632 concentration-dependently inhibited cooling-induced contraction of the gastric fundus, producing approximately 90% inhibition at a concentration of 10(-5) mol/L. Contractions were also inhibited by genistein (3 x 10(-5) mol/L), a tyrosine kinase inhibitor, but not by GF 109203X (10(-7) mol/L), a protein kinase C inhibitor. 5. Using reverse transcription-polymerase chain reaction techniques, it was observed that the mRNA for the TRPM8 receptor and Rho-kinase were expressed in the rat gastric fundus. 6. These results would suggest that cooling-induced contraction of the rat fundus is mediated by activation of TRPM8 receptors via a mechanism involving activation of Rho-kinase.

Cooling-induced contraction and protein tyrosine kinase activity of isolated arterioles in secondary Raynaud's phenomenon

To investigate the response of skin arterioles from control subjects and patients with scleroderma and Raynaud's phenomenon (RP/SSc) to cooling and modulators of protein tyrosine kinase (PTK) activity. We used the microvessel perfusion technique to characterize the response of isolated dermal arterioles (100-200 microm, outside diameter) from normal (n = 17) and RP/SSc (n = 17) subjects to cooling from 37 degrees to 31 degrees C. Fluorescent immunohistochemistry was used to measure tyrosine phosphorylation. Arterioles from control subjects exhibited dilation in response to cooling from 37 to 31 degrees C whereas those from RP/SSc subjects contracted (+4.3 +/- 1.7 vs -16.7 +/- 3.1%, P < 0.05, n = 6). In the presence of the protein tyrosine phosphatase inhibitor sodium orthovanadate (SOV, 10 microM), the response of arterioles from control subjects did not change; however, arterioles from RP/SSC subjects exhibited a significantly greater contraction (-72.6 +/- 19.7%; P < 0.05, n = 6). Tyrosine phosphorylation of arterioles at 37 degrees C from control and RP/SSc subjects was similar. In response to cooling to 31 degrees C, however, arterioles from RP/SSc subjects exhibited a significantly greater increase in tyrosine phosphorylation compared with those from control subjects (43 +/- 7.0% vs 10 +/- 3.8%; P < 0.01). SOV increased tyrosine phosphorylation in arterioles from both groups (73 +/- 11.6% vs 42 +/- 5.6%; P < 0.05, n = 5). Arterioles from RP/SSC subjects precontracted with norepinephrine exhibited greatly attenuated relaxation to acetylcholine compared with those from control subjects. The results of this study support the view that the hallmark of Raynaud's phenomenon associated with scleroderma, cooling-induced vasospasm, appears to be mediated by an increase in PTK activity possibly exacerbated by impaired endothelium-dependent vasodilation.

Increased tyrosine phosphorylation mediates the cooling‐induced contraction and increased vascular reactivity of Raynaud's disease

Increased levels of protein tyrosine kinase (PTK) are mechanistically associated with increased contractile responsiveness to cooling. This study tests the hypothesis that increased PTK activity mediates the increased vascular reactivity to agonists and cooling associated with primary Raynaud's disease (RD). The response of dermal arterioles isolated from control (n = 29) and RD (n = 29) subjects to contractile and dilatory agents at 37 degrees C and 31 degrees C was characterized using the microvessel perfusion technique. Fluorescence immunohistochemistry was used to measure tyrosine phosphorylation. At 37 degrees C, arteries from RD patients exhibited similar sensitivity to the specific alpha(2)-adrenergic agonist UK 14,304, to serotonin, and to angiotensin II. At 31 degrees C, however, the response to all 3 agonists was greater in the arterioles from the RD patients than in those from the control subjects. Agonist-induced contraction at both temperatures was reversed by cumulative addition of the PTK inhibitors genistein (1-30 microM) and tyrphostin 47 (0.1-10 microM). All arterioles from control subjects relaxed slightly in response to cooling, whereas more than half of those from RD patients contracted. This cooling-induced contraction was reversed by the cumulative addition of genistein. The 3 agonists elicited large increases in tyrosine phosphorylation only in arterial segments from RD patients at 31 degrees C. Cooling from 37 degrees C to 31 degrees C elicited a large increase in tyrosine phosphorylation in arterioles from RD patients, but not those from control subjects. All increases in tyrosine phosphorylation could be prevented by genistein. Increased tyrosine phosphorylation mediates cooling-induced contraction and the increased vascular reactivity of skin arterioles from individuals with RD.

Role of elastic fibers in cooling-induced relaxation

The objective of this work was to confirm the main role of elastic fibers in differing responses of certain vessels during cooling from 37 to 8 °C. Previous results have shown that the nature of the vessel (conduit vessel vs muscular vessel) determines the different behavior (dilatation vs contraction) of isolated vessel segments when temperature decreases from 37 to 8 °C. In this work, it has been demonstrated that vessels with a great amount of elastic fibers show a dilatation when cooling. On the other hand, muscular vessels with fewer elastic fibers, such as the renal artery, undergo a contraction. The output of calcium from intracellular stores causes contraction of the renal artery during cooling. In this vessel, vasodilatation occurs only when mechanisms of smooth muscle contraction are inactive, as is the case with vessels that have undergone a cold storage period of 48 h. The results presented in this work confirm that there are two main effects, which directly depend on the vessel origin. In conduit arteries, the decrease of temperature induces a vascular relaxation, dependent on the elastic component of the vessel wall. In muscular vessels, the predominant effect is cooling-induced contraction due to an increase of intracellular calcium. This cooling-induced contraction needs the vessel to be in optimal conditions with an active metabolism of the muscular cells. These results are a crucial issue in the sense of explaining several biomedical mechanisms where hypothermia is implicated. The type of vessel implicated in procedures, such as isolated organ perfusion, extracorporeal circulation, and bypass surgery, must be taken into account.

Paradoxical Effects of Temperature on Vascular Tone

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.

Cooling-induced bladder contraction: studies on isolated detrusor muscle preparations in the rat

Objectives. Detrusor muscle contraction and uninhibited micturition after intravesical instillation of ice water is interpreted as a sign of upper motor neuron lesions. The basic mechanism of cooling-induced contraction (CIC) at the level of smooth muscle, however, has not been satisfactorily explained. We therefore designed model experiments with cooling of rat detrusor muscle. Methods. We recorded isometric tension from strips of rat urinary detrusor muscle in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents interfering with known neurogenic (autonomic blockers, tetrodotoxin, capsaicin) and myogenic mechanisms of contraction (calcium channel blockers). Results. Stepwise cooling (37° to 5°C) of detrusor muscle induced reproducible graded contractions, inversely proportional to temperature. CIC was not dependent on a neural mechanism (not blocked by tetrodotoxin or capsaicin) or the release of neurotransmitters but was linked to translocation of calcium. It was reduced by calcium channel blockers and Ca 2+-free solution. Blockage of the Ca 2+-adenosine triphosphatase pump, which inhibits the extrusion of calcium, also plays a significant role in the process and enhances CIC. Conclusions. Cooling of detrusor muscle preparations induces a graded myogenic contraction inversely proportional to the temperature. The mechanism is not dependent on local nervous control but is related to calcium translocation.

Cooling-induced contraction of trachea isolated from normal and sensitized guinea-pigs

Fast (-7 degrees C/min) cooling of guinea-pig isolated trachea produced a rapidly developing, transient contraction followed by relaxation. Cooling-induced contraction was dependent on temperature (30, 20 or 10 degrees C) and responses in trachea obtained from actively sensitized guinea pigs were significantly greater (20 and 10 degrees C) than those observed in normal trachea. Cooling to 20 degrees C was selected for subsequent experiments. Pretreatment with sufficient concentrations of atropine, clemastine, cromoglycate, indomethacin, or nordihydroguaiaretic acid did not depress contraction to cooling in either normal or sensitized trachea. This indicates a direct effect of cooling. The contraction produced by cooling was resistant to verapamil (1 mumol/l) or dantrolene (0.3 mmol/l). Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium; all of them at 10-100 mumol/l) inhibited contraction in sensitized and normal trachea. Activators of protein kinase C (phorbol 12,13-diacetate, 1 mumol/l) enhanced while inhibitors (H-7, 20 mumol/l; staurosporine, 10 mumol/l) depressed cooling-induced contraction in both normal and sensitized tissues. Incubation (20 min) in a Ca(2+)-free solution inhibited cooling-induced contraction in normal but not in sensitized trachea. Exposure to a low Na+ (25 mmol/l) or a K(+)-free medium abolished contraction to cooling in normal and sensitized trachea. Ouabain (0.1-10 mumol/l) and vanadate (0.01-5 mmol/l) inhibited cooling-induced contraction to a greater extent in normal than in sensitized trachea. Polymyxin B (0.5 mmol/l) selectively depressed responses to cooling in sensitized trachea. In a separate series of experiments, it was shown that sensitized trachea was hyperresponsive to ouabain and vanadate. Previous cooling to 20 degrees C abolished responses to ouabain but only attenuated those to vanadate.(ABSTRACT TRUNCATED AT 250 WORDS)