Body fluid distribution in rats with cold-induced hypertension

The purpose of this experiment was to determine body fluid distribution during chronic cold exposure and to further understand the mechanism of cold-induced hypertension. Blood pressures, hematocrit, and the plasma, blood, and extracellular fluid volumes were measured in rats at intervals of 1, 3, and 5 weeks after exposure to cold (5 degrees C). Resting systolic, diastolic, and mean blood pressures measured by direct arterial cannula were significantly elevated in a time-dependent manner over the duration of cold exposure. The increase in diastolic blood pressure, which reflects the peripheral vascular resistance, exceeded that of systolic blood pressure after both 3 and 5 weeks of exposure to cold. Pulse pressure was significantly decreased by 3 and 5 weeks of cold exposure. The plasma, blood, and extracellular fluid volumes were significantly increased after both 1 and 3 weeks of exposure to cold, but had returned to control levels by 5 weeks of cold exposure. Cold exposure, however, did not affect the hematocrit. The 2-h water intake after the cold-exposed rats were returned to warm (25 degrees C) (thermogenic drinking) was significantly increased compared to that of warm-acclimated rats during the first, third, and fifth week of exposure to cold. The present results suggest that the development of cold-induced hypertension is associated with blood volume expansion, and that the elevated blood pressure is maintained by increased peripheral vascular resistance without blood volume expansion. The results also imply that exposure to cold induces a dehydration in rats.     

Hypothalamic SOCS-3 expression and the effect of intracerebroventricular angiotensin II injection on water intake and renal sodium handling in SHR

In rats, the acute central dipsogenic and natriuretic action of angiotensin II (AngII) seems to be independent of the hemodynamic effects of the peptide; however, in genetically hypertensive models, this relationship has not yet been investigated. It has been demonstrated that AngII induces the suppressor of cytokine signaling (SOCS-3) expression in the brain that, in turn, modulates further activation of the pathway, leading to desensitization to AngII stimuli with regard to its dipsogenic effect. This study investigates age-related Janus kinase (JAK-2) and SOCS-3 hypothalamic expression, by immunoblotting, and the involvement of SOCS-3 expression in urinary sodium handling and dipsogenic response in spontaneously hypertensive rats (SHR), compared with age-matched Wistar–Kyoto (WKy) rats. The intracerebroventricular (i.c.v.) application of AngII significantly enhanced the dipsogenic response, reduced C_Cr, and reciprocally promoted increased absolute and fractional rates of excretion of sodium in WKy rats. The central AngII-induced dipsogenic effect in WKy and SHR was significantly attenuated by prior i.c.v. administration of DUP753. In addition, the magnitude of the dipsogenic and renal response to AngII was significantly attenuated in age-matched SHR. Blocking of hypothalamic SOCS-3 expression by an antisense oligonucleotide resulted in partial reversal of the refractory nature of AngII in thirst responses in SHR. The altered centrally applied AngII response in SHR associated with increased hypothalamic JAK-2/SOCS-3 expression may suggest that abnormal regulation of the central angiotensin pathways may contribute to dysfunction of water–electrolyte homeostasis in SHR.     

Investigation into the specificity of angiotensin II-induced behavioral desensitization

Angiotensin II (AngII) plays a key role in maintaining body fluid homeostasis. The physiological and behavioral effects of central AngII include increased blood pressure and fluid intake. In vitro experiments demonstrate that repeated exposure to AngII reduces the efficacy of subsequent AngII, and behavioral studies indicate that prior icv AngII administration reduces the dipsogenic response to AngII administered later. Specifically, rats given a treatment regimen of three icv injections of a large dose of AngII, each separated by 20 min, drink less water in response to a test injection of AngII than do vehicle-treated controls given the same test injection. The present studies were designed to test three potential explanations for the reduced dipsogenic potency of AngII after repeated administration. To this end, we tested for motor impairment caused by repeated injections of AngII, for a possible role of visceral distress or illness, and for differences in the pressor response to the final test injection of AngII. We found that repeated injections of AngII neither affected drinking stimulated by carbachol nor did they produce a conditioned flavor avoidance. Furthermore, we found no evidence that differences in the pressor response to the final test injection of AngII accounted for the difference in intake. In light of these findings, we are able to reject these three explanations for the observed behavioral desensitization, and, we suggest instead that the mechanism for this phenomenon may be at the level of the receptor.     

Effects of long-term cold exposure on contractile muscles of rats

The effects of 20-week cold exposure on contractile properties of soleus and extensor digitorum longus (EDL) muscles and plasma hormone levels were studied in rats. Twenty male Wistar rats (5 week old) were randomly divided into 2 groups (n = 10 each): cage-control and cold-exposed. The rats in the cold-exposed group were immersed in shoulder-deep water (approximately 18 degrees C) for 1 h/d, 5 d/week, for 20 weeks. The temperature and humidity of the animal room with 12:12 h light-dark cycle were maintained at approximately 23 degrees C and 55%, respectively. The rats were pair-fed powdered diets. The electromyogram activities in soleus and EDL were elevated by cold exposure. The body weight and absolute soleus wet weight of the cold-exposed group were significantly less than controls at the end of experiment. The one-half relaxation time and contraction time of EDL were significantly longer in the cold-exposed group than in the control group. The rate of twitch tension development, normalized by the maximum twitch tension, in EDL of the cold-exposed group was less than in the control group. Further, the fatigue resistance of EDL, but not of soleus, in response to train stimulation at 10 Hz was improved by cold exposure. The plasma levels of thyroid hormones, 3,5,3'-triiodothyronine and thyroxine, were significantly greater in cold-exposed group. Similar changes were also seen in the plasma catecholamine levels in the cold-exposed group (p > 0.05). It is suggested that long-term cold exposure causes a shift of the contractile properties of fast-twitch EDL muscle toward the slow-twitch type. The results also indicated that the characteristics of muscles responded more strongly to an increased activity level than to the elevation of plasma hormones.     

The biliary-faecal excretion of thyroxine during cold exposure in the rat

1. The biliary-faecal route of thyroxine excretion has been examined by means of thyroxine labelled with (131)I in the thyroidectomized, thyroxine-maintained rat during cold exposure.2. The rate of excretion of thyroxine into the faeces is raised in rats exposed to cold for 2 weeks and fed ad libitum on a high roughage diet.3. When the faecal volumes of warm- and cold-exposed animals are made similar by controlling the roughage content of the diet the difference in their faecal thyroxine excretion rates is much reduced.4. Warm- and cold-exposed rats eating the same amount of food excrete thyroxine into their faeces at similar rates.5. Even when warm- and cold-exposed rats excrete thyroxine into their faeces at the same rate the cold-exposed animals still show a shorter half-life for blood thyroxine.6. An acceleration of the rate of loss of thyroxine from the blood is demonstrable in fasting animals within 10 hr of exposure to cold.7. Ligation of the bile-duct does not affect this acute response to cold.8. The amount of thyroxine lost into the bile within the first 8 hr after intravenous injection is similar in warm- and cold-exposed animals. The clearance of thyroxine into the bile is however greater in the cold-exposed animal since the liver is working against a lower level of blood thyroxine.9. An acceleration of the biliary-faecal route of thyroxine excretion is not the only process at work tending to reduce the biological half-life of thyroxine during cold exposure.     

Impact of maternal morphine and saline injections on behavioral responses to a cold water stressor in adult male and female progeny

The purpose of the present study was to test the effects of maternal morphine and saline injections on chronic cold water stress responses in three groups of adult male and female rats: prenatally morphine-exposed adult progeny, prenatally saline-exposed adult progeny, and control groups. All male rats were gonadally intact, and female rats were ovariectomized (OVX) in adulthood, and half of them were injected with estradiol benzoate (EB). All animals were exposed to a cold water stressor daily for 2 weeks and tested before (baseline) and after (stress effects) the chronic cold water stressor in a swim test and an open field test. In the swim test, both adult males and OVX, EB-treated adult females born to mothers injected with morphine or saline displayed more floating behavior during the swim test than their controls, both before and after the cold water stressor. Male rats exposed to morphine or saline prenatally also spent more time struggling during the swim tests than controls, and this was further increased after the cold water stressor. In the open field test, males and OVX, EB-treated females born to morphine- or saline-injected mothers were less active and displayed fewer rearings than controls. No differences were observed in OVX females as a result of prenatal injections. Thus, the present study demonstrates that maternal injections, regardless of injection content, induce long-lasting effects on stress responsiveness in adult progeny.     

Thyroxine deiodination during cold exposure in the rat

1. The urinary radio-iodide excretion following injection of [(131)I]thyroxine and tri-iodothyronine is increased in acutely cold-exposed, thyroidectomized rats.2. This cold response is demonstrable in animals which are fed or fasted or deprived of both food and water. Cold exposure does not increase the rate of urinary excretion of a tracer dose of radio-iodide. It is concluded that cold exposure accelerates the rate of deiodination of both thyroxine and tri-iodothyronine.3. It is confirmed that both adrenaline and noradrenaline administered in vivo can enhance the rate of thyroxide deiodination.4. The sympathetic blocking agents guanethidine and bethanidine reduce the extra deiodination of thyroxine induced by cold exposure. Bethanidine was also found to reduce the deiodination of tri-iodothyronine during cold.5. There is a positive correlation between the deiodination of thyroxine and the urinary catecholamine excretion in the cold-exposed but not the warm-exposed rat.6. It is suggested that the enhanced deiodination during cold exposure is mediated by the release of noradrenaline from the sympathetic nervous system.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat.

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat

The fawn-hooded (FH) rat, a strain characterized by a platelet storage-pool disease, developed focal and segmental glomerulosclerosis at the age of 2-3 months (males) and approximately 6 months (females). Male animals died spontaneously at 11-13 months, and females at 15 months of age, both with overt malignant nephrosclerosis. During the first half year of life focal glomeruli showed depositions of IgG, IgA, IgM, C3 and fibrinogen in a segmental pattern and mainly in mesangial areas. Mesangial IgG and IgA were already demonstrable at the age of 5 weeks. On electron microscopy no electron-dense deposits suggestive of immune complexes were found. Mean arterial blood pressure in 5.5-month-old male FH rats was increased compared with that of matched Wistar rats. One-year-old FH rats had severe hypertension. The presumed relationship between the hypertension, the renal lesions and the blood platelet defect is discussed.     

The effect of ghrelin on water intake during dipsogenic conditions

Ghrelin has been studied extensively in the context of food intake and energy homeostasis, but less is known about its role in other ingestive behaviors. The present studies investigated the effects of this orexigenic peptide on both food and water intake during dipsogenic conditions. Specifically, animals were exposed to one of five dipsetic stimuli: (1) 24-h water deprivation, (2) replacement of drinking water with 2.5% NaCl, (3) peripheral administration of hypertonic saline, (4) ICV injection of angiotensin II (AngII), or (5) the combination of peripheral hypertonic saline and central AngII. Animals then were given an ICV injection of ghrelin (0.5  µg) or vehicle, and subsequent food and water intakes were measured. Ghrelin reliably increased food intake under each stimulus condition. Ghrelin also affected water intake, but with less consistency across the conditions. Specifically, ghrelin attenuated water intake stimulated by acute injection of AngII or hypertonic saline, but failed to affect drinking in the other three stimulus conditions. Investigation of the temporal pattern of food and water intakes in three of these dipsogenic conditions failed to support a role of different intake patterns in the observed differences in water intake by ghrelin-treated rats. Although the effect of ghrelin on water intake was not present in every dipsogenic condition, these data provide evidence that the actions of ghrelin are not limited to food intake, but can also include alterations in water intake.     

Effects of 20-week intermittent cold-water-immersion on phenotype and myonuclei in single fibers of rat hindlimb muscles

The effects of 20 weeks of intermittent cold-water-immersion on myosin heavy chain (MHC) expression,cross-sectional area (CSA), myonuclear number, and myonuclear domain size in isolated single fiber of soleus and extensor digitorum longus (EDL) muscles were studied in male Wistar rats. Cold exposure was accomplished by submerging the rats in shoulder-deep water, maintained at approximately 18 degrees C, for 1 hour/day, 5 days/week and for 20 weeks. Cold exposure resulted in a significant inhibition of body and soleus muscle weight gain. The percent type IIa MHC fibers of EDL muscle was increased, whereas that of type IIa + b MHC fibers was less in cold-exposed group than controls (p < 0.05). The mean CSA and myonuclear number in type I MHC fibers of soleus muscle in cold-exposed group were significantly less than controls. Myonuclear domain in type IIa fibers of EDL in the cold-exposed group was greater than controls (p < 0.05). It is suggested that prolonged cold exposure causes the fiber-type-specific adaptation in rat hindlimb muscles. It is further indicated that cold-exposure-related modulation of myonuclear number was closely related to reduction of fiber CSA, not the shift of fiber phenotype.     

Comparative Dynamics of Salmonella Infection After Primary and Secondary Challenge of Mice Exposed to 10 and 23 C

Mortality of mice increased significantly as a result of cold exposure when the animals were challenged orally with Salmonella typhimurium, strain RIA. As reported earlier, cold exposure alone did not kill control animals nor did oral challenge at room temperature. No differences were apparent in the number of Salmonella per gram of liver-spleen, colon, or lung between groups of infected mice housed at 23 and 10 C. The number of bacteria increased equally in liver-spleen samples during the period of increasing mortality in the group housed at 10 C and the period of overt illness in those housed at 23 C. The ability to clear the bloodstream of a secondary intravenous challenge did not seem to be impaired by cold exposure. The bacterial load in the spleen and the rate of change in weight of that organ was equal in animals given a secondary challenge at 10 or 23 C. However, the absolute spleen weight was less in the cold-exposed group as was survival when the secondary challenge was administered 3 days after the primary oral challenge. The studies indicate that endotoxin from S. typhimurium may sensitize mice to the lethal effects of cold exposure. The increase in mortality observed in cold-exposed, infected mice is not due to greater bacterial proliferation in these animals. Rather, the combined stress effects of the bacterial agent(s) and cold may link lympholytic effects to impaired detoxification and increased energy demands, which often leads to lethal vascular collapse in cold-exposed, infected mice.     

Cardiovascular, neuropeptide Y, and adrenergic responses in stress are sexually differentiated

Cardiovascular and sympatho-adrenomedullary responsiveness at rest and during stress were studied in weight-matched, sexually mature male and female rats. At rest, although there were no sex differences in cardiovascular parameters, females had two-fold higher plasma levels of norepinephrine (NE) and epinephrine. Resting plasma levels of neuropeptide Y-immunoreactivity (NPY-ir, a putative sympathetic cotransmitter and a vasoconstrictor) were similar in both sexes. Stresses of handling and cold (4 degrees C) water exposure induced greater pressor and tachycardic responses in males than in females. Males but not females exhibited a protracted recovery from the stress-induced pressor responses and a 2-fold increase in plasma NPY-ir suggesting that NPY release is sexually differentiated. Only in males, low basal plasma NE and NPY-ir levels inversely correlated with greater cold-induced pressor responses. Furthermore, in areflexic pithed rats, pressor adrenergic and NPY responses were greater in males than in females suggesting the possibility of "down"-regulation of vascular adrenergic receptors in females (due to elevated circulating catecholamines) and "up"-regulation of NPY and adrenergic receptors in males.     

Altered responses to environmental stress in streptozotocin-diabetic rats.

Metabolic and biochemical adaptations were compared in streptozotocin-diabetic and nondiabetic control rats exposed for 24 hours to a cold environment (4 degrees C) or hypobaric hypoxia (simulated altitude = 12,000 ft). In the cold, diabetic rats had greater reductions in adrenal norepinephrine (NE) and greater elevations in urinary NE and epinephrine excretion. However, diabetics did not increase food intake, whereas cold-exposed nondiabetic rats did. 5-HT turnover was reduced in hypothalamus and elevated in brain stem in both diabetics and nondiabetics. Responses to hypoxia were different. Both diabetics and nondiabetics reduced food and water intake and had elevated plasma glucose concentrations. Diabetics had elevated urinary NE excretion. Hypothalamic NE concentration and dopamine turnover were significantly reduced by hypoxia. Brain stem 5-HT turnover was also reduced in nondiabetics but not in diabetics. Thus, diabetics had a different response profile to the environmental stressors than nondiabetics. In addition, the two stressors elicited different responses. Some stressors may be more debilitating in diabetics. The greater reactivity of the sympathetic nervous system in diabetics suggests a mechanism by which stress leads to increased risk of metabolic complications in diabetes mellitus.     

壮侗语族族群高血压现况及其生化指标值分析

目的 探讨中国壮侗语族族群高血压患病率及生化指标的特点。 方法 对壮侗语族5个族群7411例（男性3248例，女性4163例）进行血压测量及生化指标检测。 结果 壮侗语族各族群之间高血压患病率差异具有统计学意义。壮侗语族族群同年龄组男性高血压患病率高于女性，男性、女性收缩压、舒张压均随年龄增长而升高，高血压患病率也随年龄增长而升高。壮侗语族族群男性甘油三酯、胆固醇、低密度脂蛋白均值均低于女性。高血压患者血尿酸、血尿素、血脂均值明显高于血压正常者，高血压患者与血压正常者胆红素、血清蛋白均值接近，高血压患者血脂均值多超出正常范围。 结论 壮侗语族族群高血压患病率较高，高血压患者要注意自身血尿酸、血尿素、血脂的增高。     

Effect of Age and Sex on Blood Pressure,Development of Renal Hypertension,and Concentration of Nitric Oxide in the Blood of Albino Rats

The mean blood pressure did not depend on the sex of animals and was characterized by the same ontogenetic changes in males and females. The mean blood pressure in infantile and, particularly, in old rats was higher than in adult animals. The increase in blood pressure in old rats was accompanied by a decrease in NO production. Infantile rats were least resistant to the development of renal hypertension. The degree of hypertension in infantile and adult females was lower than in males. However, the concentration of NO in these females was higher than in male rats. Aging was accompanied by inversion of sex differences in the resistance to renal hypertension. The severity of hypertension in old females was greater than in males. It was accompanied by a signifi cant age-related decrease in NO concentration in female animals. Our results indicate that NO plays an important role in sex differences in the resistance of infantile, adult, and old rats to hypertension, while the decrease in NO concentration during aging leads to blood pressure elevation in females and males.     

Effect of chronic developmental lead exposure on cell-mediated immune functions.

Studies were performed to investigate the effects of chronic, low level pre- and post-natal lead exposure on cell-mediated immune function in rats. Weanling female rats were exposed to lead (as lead acetate) in their drinking water at 0, 25, and 50 ppm for 7 weeks. At the end of 7 weeks they were mated with untreated males and continued on the same dosage throughout gestation and lactation. The offspring of these females were weaned at 21 days of age and continued on the same lead exposure regimen as their mothers. These offspring were used in immune surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to mitogen stimulation and in reduced delayed hypersensitivity responsiveness. Results indicate that chronic low-level lead exposure causes suppression of cell-mediated immune function.     

Sex differences in the basal firing rate and the responsiveness to opioid peptides of rat hippocampal neurons.

The basal firing rate and the responsiveness to dynorphin and leu-enkephalin of the neurons in the pyramidal cell layer of the hippocampus were studied in intact male, castrated male, castrated female, and castrated female rats injected s.c. with 20 micrograms estradiol benzoate (EB) for 3 days. Most of the neurons studied had low spontaneous firing rate (less than 5 Hz) and burst-like activity in all the groups. The basal firing rates in castrated males and females were not different from those in intact males and castrated females treated with EB, respectively. However, neurons in intact and castrated males had significantly higher firing rates than those in castrated females with and without EB treatment, respectively. When effective, both iontophoretically applied dynorphin and leu-enkephalin evoked predominantly excitatory responses. Either castration of males or EB treatment to castrated females did not affect the neuronal responsiveness to these peptides. On the other hand, the responsiveness of neurons to leu-enkephalin, but not to dynorphin, was significantly different between castrated male and female rats. These results suggest that sex steroids do not affect the basal firing rate as well as the responsiveness to opioid peptides of the pyramidal cells in the hippocampus in adult animals. However, sex differences in the basal firing rate and in the responsiveness to leu-enkephalin might account for the differences in hippocampal functions between male and female rats.     

Endocrine response to acute cold exposure by lactating and non-lactating Norway rats

Plasma levels of corticosterone, prolactin and thyroxine (T4) were measured in lactating and non-lactating Norway rats at 22 degrees C and 4 degrees C. Acute cold exposure increased corticosterone secretion in all groups, although non-lactating female levels rose higher than those of mother rats. While prolactin levels are unaffected by acute cold exposure in non-lactating females, mothers with their litters had lower prolactin levels in the cold. T4 levels increased during cold exposure in lactating females, suggesting that the low T4 levels observed during lactation may not be due to lactational competition for available iodine.     

Sex differences in relation to conditioned fear-induced enhancement of morphine analgesia

A number of studies have reported that both the immediate and proactive effects of exposure to a shock stressor are less pronounced in female than in male rats. A separate area of research has demonstrated that female rats are less sensitive to the analgesic effects of morphine than males. Experiments from our laboratory, as well as others, have found that exposure to a context associated with shock (i.e., conditioned fear context) at the time of morphine administration, enhances the analgesic effects of morphine. Since previous studies have exclusively employed male rats, the purpose of Experiment 1 was to determine if a sex difference exists to this context conditioned fear-induced enhancement of morphine-induced analgesia. The findings of Experiment 1 showed that females do not appear to exhibit conditioned fear-induced enhancement of morphine analgesia as compared to males. Experiment 2 demonstrated that females exhibited higher levels of conditioned fear-induced enhancement of morphine analgesia during diestrus I than estrous. Experiment 3 demonstrated that females exhibited lower levels of conditioned analgesia compared to males, while both groups exhibited similar freezing levels. The findings of the present experiments suggest that the sex difference observed in Experiment 1 may be due to differences in conditioned analgesia.