Heat acclimation and hypohydration in aged rats: The involvement of adrenergic pathways in thermal-induced vasomotor responses in the portal circulation

1. 1. The beneficial effects of heat acclimation on thermal induced vasomotor responses of hypohydrated aged rats were assessed by measuring the isometric tension of aortic and portal rings of old and young rats under heat acclimation and hypohydration in response to -adrenergic (-AR) and β-adrenergic (β-AR) stimulation (phenylephrine 10⁻⁹–10⁻² mM and isoprenaline 10⁻⁹–10⁻⁴ respectively). In parallel, portal blood flow (PBF), which drains the splanchnic vasculature, was measured in conscious rats, before and during heat stress (42°C).

2. 2. In the aorta, heat acclimation augmented phenylephrine (-AR) induced tension, to a great extent in the older rats. Hypohydration increased -AR sensitivity in all experimental groups. Acclimation and aging brought about decreased responsiveness in isoprenaline induced relaxation (β-AR) in both the aorta and the portal vein. Hypohydration increased β-AR responsiveness in the portal vein of OR, acclimated and acclimated-hypohydrated rats.

3. 3. Normothermic euhydrated resting PBF was similar for young and old rats. Hypohydration decreased resting PBF. Upon heat stress, thermal induced vasoconstriction in hypohydrated YR and OR occurred earlier than in the euhydrated groups and was more pronounced. The latter responses were attenuated in the old rats.

4. 4. Taken together, these results imply that chronic environmental stressors such as heat acclimation and hypohydration produce selective alterations in AR responsiveness of the vasculature in both young and old rats. Consequently, thermoregulatory vasomotor mediated mechanisms, as exhibited in this study in PBF, may differ in their responsiveness in these two age groups.

     

Redistribution of cardiac output in anesthetized thermally dehydrated rats

Cardiac output (CO) and its distribution were studied in dehydrated (37 degrees C) anesthetized (Na thiopentone) rats prior to and following heat acclimation (at 34 degrees C), using 57Co 15 micron microspheres. In non-acclimated dehydrated rats, CO decreased while heart rate (HR) increased significantly. Following acclimation CO increased without any change in HR; during dehydration CO remained elevated together with a significant increase in HR. In non-acclimated rats at low dehydration blood perfusion to peripheral thermoregulatory areas increased while perfusion of splanchnic area decreased; at high dehydration level peripheral blood flow decreased whereas splanchnic blood flow was augmented. In acclimated dehydrated rats, CO distribution to thermoregulatory areas did not change while perfusion of the splanchnic area decreased. It is suggested that following acclimation, the increased CO contributes to maintenance of thermoregulatory peripheral blood flow; in non-acclimated rats severe dehydration leads to augmented blood flow in the permeable splanchnic vascular bed, increasing efflux of plasma protein and failure of plasma volume conservation.     

Skeletal muscle metabolism during exercise is influenced by heat acclimation

The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment.     

The effect of constant and changing temperatures on the thermal resistance of Lymnaea peregra (Müller)

The effect of constant and changing temperatures on both high and low lethal temperatures of Lymnaea peregra and the time course of acclimation were investigated. Snails acclimated to 6.5°, 11.5° and 16.5°C showed paradoxical ‘adaptation’ of their high letal temperature and reasonable ‘adaptation’ of the lowlethal temperature. This combination is thus observed for the first time in molluscs. Seasonal variation in the upper lethal temperature showed parallel changes and the snails became less resistant to heat during spring and summer. Acclimation to changing temperature conditions did not extend their temperature tolerance range. During the course of acclimation of 6.5°C snails to 16.5°C, about 70% of the acclimation was completed within the first 24 h and the rest was completed within 360 h at 16.5°C.     

Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.     

Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

Nitric oxide (NO) participates in locally mediated vasodilation induced by increased local skin temperature (T(loc)) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS (eNOS) participates in the former, but not the latter, response. We tested this hypothesis by examining the effects of the eNOS antagonist N(G)-amino-l-arginine (l-NAA) on skin blood flow (SkBF) responses to increased T(loc) and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with l-NAA in Ringer solution and a second site with Ringer solution alone. SkBF [laser-Doppler flowmetry (LDF)] and blood pressure [mean arterial pressure (MAP)] were monitored, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF / MAP). In protocol 1, T(loc) was controlled with LDF/local heating units. T(loc) initially was held at 34 degrees C and then increased to 41.5 degrees C. In protocol 2, after a normothermic period, whole body heat stress was induced (water-perfused suits). At the end of both protocols, 58 mM sodium nitroprusside was perfused at both microdialysis sites to cause maximal vasodilation for data normalization. In protocol 1, CVC at 34 degrees C T(loc) did not differ between l-NAA-treated and untreated sites (P > 0.05). Local skin warming to 41.5 degrees C T(loc) increased CVC at both sites. This response was attenuated at l-NAA-treated sites (P < 0.05). In protocol 2, during normothermia, CVC did not differ between l-NAA-treated and untreated sites (P > 0.05). During heat stress, CVC rose to similar levels at l-NAA-treated and untreated sites (P > 0.05). We conclude that eNOS is predominantly responsible for NO generation in skin during responses to increased T(loc), but not during reflex responses to whole body heat stress.     

Acclimation to temperature and death at changing lethal temperatures in the freshwater fish Chalcalburnues chalcoides

1. 1.|In the freshwater fish Chalcalburnus chalcoides, an increase in the body (standard) size caused decreases in the upper LT-50 from 36.6° to 36.0°C and lower LT-50 from 6.3° to 5.3°C

2. 2.|The fish acclimated to constant temperatures between 10°C and 30°C showed reasonable heat acclimation and also reasonable cold acclimation. Thus, an increase in the acclimation temperature from 10°C to 30°C caused increases in the upper LT-50 from 34° to 36.2°C and the lower LT-50 from 1.25 to 6.5°C.

3. 3|The mean survival time — temperature curves of 10°, 20° and 30°C acclimated fish at various constant temperatures showed decreased in the survival tim ewith increasing lethal temperatures. Furthermore, an increase in the acclimation temperature causes a shift in the survival duration-temperature curve to the right, i.e., the fish become more heat resistant. Thus, the mean survival duration of 10°, 20° and 30°C acclimated fish at 35°C were 7.5, 79.6 and 530 minutes, respectively.

4. 4.|The effect of the thermal experience to changing lethal temperatures depends on the first lethal temperature to which the fish were exposed as well as the sequence of temperature changes. In the experiments in which the first lethal temperatures were between 32° and 34°C and the temperature was varied in an ascending order, their thermal resistance was increased and the fish required 114 to 174% of the expected lethal doses to die while in the experiments in which the starting temperature were between 38° and 40°C and the temperature varied in descending order, the fish become more sensitive to the upper lethal temperature and they died after receiving only 62 to 81% of the expected lethal doses. Thus, with a gradual increase in the lethal temperature, the fish show additional acclimation in the zone of resistance which in turn causes an increase in the thermal resistance. This may have ecological significance in nature.

Short- and long-term responses to fescue toxicosis at different ambient temperatures

Intake of endophyte-infected tall fescue by cattle results in fescue toxicosis, which is characterized by increased hyperthermia during heat stress and concomitant reductions in feed intake and growth. Rats were monitored at 21 or 31 °C for short- or long-term periods to determine temporal changes associated with the intake of endophyte-infected (E+) or uninfected (E−) fescue seed diets. Core temperature only changed in rats fed E+ diet at 31 °C. Intake of E+ diet reduced feed intake, daily gain, and serum prolactin. There were temporal and thermal differences in the response to endophytic toxins, with short-term changes diminishing over time at 21 °C, but increasing for certain parameters at 31 °C.     

Vascular effects of red wine polyphenols in chronic stress-exposed Wistar-Kyoto rats

Present study investigated the effect of red wine polyphenolic compounds (Provinols) on blood pressure (BP), nitric oxide synthase (NOS) activity and vascular function in Wistar-Kyoto (WKY) rats exposed to chronic social stress produced by crowding. Adult male rats were divided into four groups: control (480 cm(2)/rat), Provinols-treated (20 mg/kg/day, 480 cm(2)/rat), crowded (200 cm(2)/rat) and crowded treated with Provinols (20 mg/kg/day, 200 cm(2)/rat) for 8 weeks. No differences in BP were observed among the groups at the end of experiment, however, reduced BP was observed in Provinols-treated rats after 3 weeks of treatment. NOS activity in the aorta was significantly elevated in crowded rats, while Provinols alone had no effect on nitric oxide (NO) production. Acetylcholine-induced relaxation of the femoral artery was significantly improved in stressed and Provinols-treated rats vs. control, without significant changes in their noradrenaline-induced vasoconstriction. Interestingly, Provinols blunted the elevation of NO production and vasorelaxation during crowding. Increased endothelium-dependent vasorelaxation and NO synthesis in crowded rats may represent the adaptation mechanisms, resulting in unaltered blood pressure in stress-exposed normotensive rats. This study further demonstrated that elevated release of NO during chronic stress may be prevented by Provinols. Thus, Provinols might maintain equilibrium between endothelium-derived vasoconstrictor and vasodilator factors in stress.     

Heat acclimation increases skin vasodilation and sweating but not cardiac baroreflex responses in heat-stressed humans.

In the present study, to test the hypothesis that exercise-heat acclimation increases orthostatic tolerance via the improvement of cardiac baroreflex control in heated humans, we examined cardiac baroreflex and thermoregulatory responses, including cutaneous vasomotor and sudomotor responses, during whole body heating before and after a 6-day exercise-heat acclimation program [4 bouts of 20-min exercise at 50% peak rate of oxygen uptake separated by 10-min rest in the heat (36 degrees C; 50% relative humidity)]. Ten healthy young volunteers participated in the study. On the test days before and after the heat acclimation program, subjects underwent whole body heat stress produced by a hot water-perfused suit during supine rest for 45 min and 75 degrees head-up tilt (HUT) for 6 min. The sensitivity of the arterial baroreflex control of heart rate (HR) was calculated from the spontaneous changes in beat-to-beat arterial pressure and HR. The HUT induced a presyncopal sign in seven subjects in the preacclimation test and in six subjects in the postacclimation test, and the tilting time did not differ significantly between the pre- (241 +/- 33 s) and postacclimation (283 +/- 24 s) tests. Heat acclimation did not change the slope in the HR-esophageal temperature (Tes) relation and the cardiac baroreflex sensitivity during heating. Heat acclimation decreased (P < 0.05) the Tes thresholds for cutaneous vasodilation in the forearm and dorsal hand and for sweating in the forearm and chest. These findings suggest that short-term heat acclimation does not alter the spontaneous baroreflex control of HR during heat stress, although it induces adaptive change of the heat dissipation response in nonglabrous skin.     

Heat acclimation in rats: modulation via lipid polyunsaturation

Heat acclimation of rats has been shown to enhance endurance of rat hearts to ischemic insult and acute heat stress. Common protective features have been shown to be operative during both these stress-inducing conditions. To explore the role of membrane lipid composition in the adaptive response, we analyzed two major parameters that impact membrane dynamics and order, the nonesterified cholesterol levels and the acyl chain composition of phospholipids, in rat heart and salivary glands, both major thermoregulatory organs, in short- and long-term heat-acclimated rats. Before exposure to heat, control salivary gland tissue has a higher cholesterol-to-phospholipid mole ratio (0.32 +/- 0.02) than heart (0.14 +/- 0.01), and the acyl chains of its phospholipids are 50% more saturated. The remodeling strategies of the tissues after exposure to heat differed. Heart cholesterol levels increased after short-term heat acclimation (approximately 50%), whereas salivary gland cholesterol levels decreased in acute heat stress and long-term heat acclimation (approximately 32%). Remodeling of phospholipid acyl chains, particularly an increase in docosahexaenoic acid, was a protective strategy in both tissues (57% in heart and >100% in salivary glands). Modifying membrane lipid composition by treating rats with liposomes composed of egg phosphatidylcholine (PC) before exposure to heat resulted in a 38% increase in endurance to thermal stress. The density and affinity of muscarinic receptors of submaxillary salivary glands, involved in the acclimation response, were measured in control and PC liposome-treated rats, and then both groups were subjected to short-term heat acclimation. After PC treatment the well-established compensatory upregulation of the muscarinic receptors and concomitant decrease in their affinity was blunted. The substantial increase in the thermal endurance of heat-challenged intact rats after treatment with PC liposomes (600 vs. 200 min) suggests that membrane lipid composition plays a role in the ability of these tissues to respond to heat stress.     

Thermal acclimation, hydroperoxide detoxifying enzymes and oxidative stress in the lung and liver of Rana perezi

1. 1.Rana perezi adult frogs were acclimated to cold (10 ± 2°C) and warm (29 ± 1°C) temperatures for 4 months.

2. 2.After acclimation, a partial compensation of the oxygen consumption of the animals was found because of a reduction of its thermal sensitivity.

3. 3.Activities of liver and lung catalase, selenium (Se)-dependent and Se-independent glutathione peroxidases were not changed by thermal acclimation.

4. 4.Tissue peroxidation (TBA-RS) increased in the liver of heat acclimated animals.

5. 5.Hydroperoxide detoxifying enzyme activities did not show inverse compensation of temperature during acclimation. It is proposed that the pattern of thermal compensation shown by these enzymes in different species depends on a variety of factors including: (a) the thermal sensitivities of hydroperoxide producing and scavenging systems; (b) the changes induced by acclimation in the rate of hydroperoxide generation.

No effects of acclimation to heat on immune and hormonal responses to passive heating in healthy volunteers

Heat acclimation results in whole body-adaptations that increase heat tolerance, and might also result in changed immune responses. We hypothesized that, after heat acclimation, tumor necrosis factor alpha, interleukin 6 and the lymphocyte count would be altered. Heat acclimation was induced in 6 healthy men by 100 min of heat exposure for 9 days. Heat exposure consisted of (1) 10 min of immersion up to chest-level in water at 42°C and (2) 90 min of passive heating by a warm blanket to maintain tympanic temperature at 37.5°C. The climatic chamber was maintained at 40°C and a relative humidity of 50%. Blood samples were analyzed before and after heat acclimation for natural killer (NK) cell activity, counts of lymphocytes B and T, before and after heat acclimation for peripheral blood morphology, interleukin 6, tumor necrosis factor alpha, and cortisol. A Japanese version of the profile of mood states questionnaire was also administered before and after acclimation. The concentrations of white blood cells, lymphocytes B and T, cortisol, interleukin 6, tumor necrosis factor alpha and NK cell activity showed no significant differences between pre- and post-acclimation, but there was a significantly lower platelet count after acclimation and, with the profile of mood states questionnaire, there was a significant rise in anger after acclimation. It is concluded that heat acclimation by passive heating does not induce alterations in immune or endocrine responses.     

长期高饱和、高不饱和脂肪酸饮食诱导胰岛素抵抗大鼠肾动脉舒张和收缩功能的变化

本文旨在探讨长期高饱和、高不饱和脂肪酸饮食诱导胰岛素抵抗（insulin resistance,IR）大鼠。肾动脉舒张和收缩功能的变化。成年Wistar大鼠随机分为对照组、高饱和脂肪酸组和高不饱和脂肪酸组,每组14只。喂养6个月后,用高胰岛素正常葡萄糖钳夹技术的葡萄糖输注率（glucose infusion rate,GIR）评价IR;用尾套法测定大鼠血压,同时比较三组大鼠的体重、血清甘油三酯、游离脂肪酸、胰岛素、空腹血糖和NO代谢产物NO2-／NO3-。大鼠处死后,取肾动脉放入生理盐溶液中,观察血管对各种因子的舒、缩反应。结果显示,喂养6个月后,与对照组大鼠比较,高饱和脂肪酸组和高不饱和脂肪酸组大鼠均出现血压升高、血清甘油三酯升高和胰岛素敏感性降低;体重、空腹血糖、胰岛素和游离脂肪酸均升高（P〈0．01）：而两高脂组间体重、空腹血糖、胰岛素和游离脂肪酸无显著性差异。高饱和脂肪酸组大鼠肾动脉对ACh的内皮依赖性最大舒张反应（Rmax）最低,其次为高不饱和脂肪酸组和对照组：对照组与两高脂组有显著性差异（P〈0．01）,而两高脂组间无显著性差异。血管经L-Arg孵育后,两高脂组肾动脉对ACh的内皮依赖性Rmax均比孵育前增加,经N^ω-吐硝基-L-精氨酸（N^ω-nitro-L-arginine,L-NNA）及美蓝（methyleneblue,MB）孵育后,两高脂组Rmax均比孵育前降低（P〈0．05,P〈0．01）;对照组各孵育液之间无显著性差异（P：〈0．05）。肾动脉对硝普钠的非内皮依赖性Rmax及对去甲肾上腺素的收缩反应,三组间无显著性差异（P〈0．05）。相关分析结果显示,肾动脉对ACh的内皮依赖性Rmax与收缩压、甘油三酯呈明显负相关,与NO2-／NO3-和GIR呈明显正相关,游离脂肪酸与N02-／NO3-呈明显负相关。结果提示,高饱和及高不饱和脂肪酸饮食均可引起高血压及与之密切相关的内皮依赖性血管舒张功能减弱、高脂血症和IR,高脂诱导内皮依赖性血管舒张功能减弱与L-Arg-NO-cGMP通路受损有关。     

Cardiovascular and thermoregulatory responses to repeated anticholinesterase administration

1. 1.|Pyridostigmine administration decreased resting heart rate by 11 ± 7 beats/min and resting oesophageal temperature by 0.23 ± 12°C after 50 h (P < 0.05). In addition, red blood cell cholinesterase activity was decreased an average of 43 ± 7% after 50 h of pyridostigmine treatment.

2. 2.|The lower heart rates and core temperatures at rest were continued during high intensity exercise in a 35°C environment. Whole body sweating was 12 ± 18% higher (P = 0.20) during exercise in the heat after 50 h of pyridostigmine treatment.

3. 3.|Repeated anticholinesterase administration had little effect on cardiovascular and thermoregulatory responses during high intensity exercise.

Exercise in the heat: Effects of dinitrophenol administration

1. 1.|Dinitrophenol (DNP) was administered to rats in two equal dosages (20 mg/kg, 30 min interval); the second injection was followed immediately by exercise (9.14 m/min) in the heat (30°C) or at room temperature (21°C).

2. 2.|At 21°C control (saline-treated) rats manifested a mean endurance of 94 min which was reduced to 32 min among DNP-treated animals.

3. 3.|At 30°C, control rats ran for 65 min (δT_re/min = 0.05°C) while DNP-treated animals had a mean endurance of only 12 min (δT_re/min = 0.22°C).

4. 4.|DNP-treated rats (30°C) manifested no decrements in tail-skin heat loss (δT_sk/min = 0.17°C vs 0.10°C) or saliva secretion (0.78 g/min, DNP vs. 0.19 g/min, control) for their brief treadmill duration.

5. 5.|The increased metabolic heat production of DNP severely reduced performance.

Effects of Hydration Level and Heat Stress on Thermoregulatory Responses,Hematological and Blood Rheological Properties in Growing Pigs

Heat stress is one of the major limiting factors of production efficiency in the swine industry. The aims of the present study were 1) to observe if hemorheological and hematological parameters could be associated to physiological acclimation during the first days of heat stress exposure and 2) to determine if water restriction could modulate the effect of thermal heat stress on physiological, hematological and hemorheological parameters. Twelve Large White male pigs were divided into an ad libitum and a water restricted group. All pigs were submitted to one week at 24°C (D-7 to D-1). Then, at D0, temperature was progressively increased until 32°C and maintained during one week (D1 to D7). We performed daily measurements of water and feed intake. Physiological (i.e., skin temperature, rectal temperature, respiratory rate), hematological and hemorheological parameters were measured on D-6, D-5, D0, D1, D2 and D7. Water restriction had no effect on physiological, hematological and hemorheological parameters. The first days of heat stress caused an increase in the three physiological parameters followed by a reduction of these parameters suggesting a successful acclimation of pigs to heat stress. We showed an increase in hematocrit, red blood cell aggregation and red blood cell aggregation strength during heat stress. Further, we observed an important release of reticulocytes, an increase of red blood cell deformability and a reduction of feed intake and blood viscosity under heat stress. This study suggests that physiological acute adaptation to heat stress is accompanied by large hematological and hemorheological changes.     

Involvement of nitric oxide in acquired thermotolerance of rice seedlings

The role of nitric oxide (NO) in thermotolerance acquired by heat acclimation (38°C) was investigated. Results showed that 38°C acclimation, on the one hand, obviously reduced hydrogen peroxide (H₂O₂) and MDA contents and ion leakage degree in rice leaves; however, on the other hand, it increased the survival of rice (Oryza sativa L.) seedlings under 50°C heat stress. Application of nitric oxide donor, sodium nitroprusside (SNP), prior to 38°C acclimation dramatically increased the acquired thermotolerance. To elucidate the role of endogenous NO in acquired thermotolerance, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO, a specific NO scavenger) was used (scavengers are used to control the level of both exogenous and endogenous NO). Results showed that PTIO pretreatment resulted in the elimination of acquired thermotolerance induced by 38°C acclimation in rice seedlings. Nitric oxide (NO) release measurement indicated that there was indeed an abrupt elevation in the NO content in 40 min after 38°C acclimation, proving the involvement of NO in acquired thermotolerance inducement in rice seedling.