Cardiovascular concomitants of ultrasound production during cold exposure in infant rats

Two experiments explored the cardiovascular consequences of extreme cold exposure and their relationship with ultrasound production in infant rats. Experiment 1 addressed the thermoregulatory and cardiovascular concomitants of ultrasound production during cold exposure in rats pretreated with saline or the ganglionic blocker chlorisondamine (5 mg/kg). For both groups, emission of ultrasound was associated with hypothermia and bradycardia. Experiment 2 explored whether the hypothermia experienced by pups in Experiment 1 is associated with increased blood viscosity, which is an important factor affecting venous return to the heart. Blood viscosity increased significantly as temperature decreased from 38 degrees C to 22 degrees C. These experiments suggest that, during extreme cold exposure, decreased cardiac output and increased blood viscosity combine to diminish venous return. The authors have hypothesized that pups respond to decreased return by recruiting the abdominal compression reaction, a physiological maneuver that propels blood back to the heart, resulting in emission of ultrasound as an acoustic by-product.     

Food intake and peripheral factors after recovery from insulin-induced hypoglycemia

Rats increased food intake after plasma glucose returned to normal in the wake of an insulin-induced hypoglycemic episode. Whereas increased eating 6-8 h after insulin occurred only when plasma glucose levels fell below 70 mg/dl, intakes were not related to the degree of prior hypoglycemia. Administration of glucose in the first 3 h after insulin prevented increased eating, whereas glucose given 4-6 h after insulin was less effective. Intravenous infusions of fructose given in the first 3 h after insulin injection prevented increased food intake in normal but not hepatic-vagotomized rats. Determination of various metabolic variables in parallel experiments showed that insulin treatment resulted in changes in peripheral metabolism, which persisted at the time feeding tests were conducted, and that administration of glucose or fructose tended to reverse these changes. The results suggest that increased food intake after recovery from hypoglycemia is associated with peripheral metabolic consequences of ongoing or previous counterregulatory responses which occur during hypoglycemia and that alterations in hepatic metabolism are sufficient to inhibit this insulin-induced eating.     

Hormonal changes during experimental hypothalamic obesity in rats

Conclusions The following changes were observed in rats with experimental hypothalamic obesity: an enhancement in the function of the pancreatic insular apparatus; an increase in hypophyseal STH biosynthesis and secretion; a decrease in hypophyseal thyrotropic function and thyroid gland activity, with disturbances in thyroid hormone metabolism in target tissues; lack of changes or a decrease in adrenal glucocorticoid function; an enhancement of lipogenesis; a decrease in the content of cAMP in a number of organs and tissues.Translated from Problemy éndokrinologii, Vol. 24, No. 1, pp. 55–60, January–February, 1978.     

Sympatho-adrenal activity of SHR and WKY rats during recovery from forced immobilization

Circulating levels of norepinephrine (NE), epinephrine (EPI), dopamine-β-hydroxylase (DBH), and corticosterone were compared in spontaneously hypertensive (SHR) and Wistar-Kyoto normotensive (WKY) rats during recovery from a 2-hr period of immobilization stress. On the day before the experiments, a catheter was inserted into the ventral caudal artery of each rat to measure directly blood pressure and heart rate and to obtain samples of blood from conscious, unhandled rats. Immediately prior to the period of forced immobilization, while animals were at rest in their home cages, plasma levels of NE and EPI did not differ between rats of the 2 strains. After 2 hr of immobilization, circulating levels of NE, EPI, and DBH were significantly higher in SHR rats than in WKY rats. In contrast, increments in mean blood pressure after 2 hr of stress were greater in WKY rats. When compared to WKY rats, SHR rats had significantly higher circulating levels of NE, EPI, and DBH for up to 4 hr after the period of immobilization. These results are consistent with the view that the sympatho-adrenal medullary system of SHR rats is more responsive than WKY rats to immobilization stress. In addition, in SHR rats, the sympatho-adrenal system remains in a heightened state of activity for a longer period of time following stressful stimulation. The excessive and prolonged discharge of catecholamines into the circulation during stress may be an important factor in the etiology of this form of experimental hypertension.     

Ovarian hormone status and skeletal muscle inflammation during recovery from disuse in rats

Resumption of normal muscle loading after a period of disuse initiates cellular processes related to mass accretion. The renewed loading also induces a significant amount of muscle damage and subsequent inflammation. Ovarian hormone depletion delays atrophied myofibre mass recovery. Ovarian hormones are also global regulators of immune system function. The purpose of this study was to determine whether ovarian hormone depletion-induced deficits in myofibre regrowth after disuse atrophy are related to the induction of muscle damage and the associated inflammatory response. We hypothesized that soleus muscle immune cell infiltration and inflammatory gene expression would be both accentuated and prolonged in ovarian hormone-depleted rats during the first week of recovery from disuse atrophy. Intact and ovariectomized (OVX) female rats were subjected to hindlimb suspension for 10 days and then returned to normal ambulation for a recovery period, the rats were killed and the soleus muscle removed for analysis. Although reloading increased both circulating creatine kinase and myofibre membrane disruption, there was no effect of ovarian hormones on these processes during recovery. Muscle neutrophil concentration was increased above baseline regardless of hormone status at days 1 and 3 of recovery; however, this increase was 43% greater at day 3 in the OVX group. Muscle ED1+ and ED2+ macrophage concentrations were increased during recovery in both groups. However, macropage concentrations remained elevated at day 7 of recovery in the OVX group, whereas they returned to control levels in the intact group. Cyclo-oxygenase-2, interleukin-6 and interleukin-1beta muscle mRNA expression increased similarly during recovery, regardless of ovarian hormone status. These results demonstrate that the initial myofibre damage and inflammatory gene expression induced during muscle recovery from disuse atrophy are independent of ovarian hormone status.     

Impaired hypophagia induced by fecal anorexigenic substance in Zucker obese rats

Influence of fecal anorexigenic substance (FS-T) on feeding by Zucker obese rats was compared to that by their lean littermates and Wistar King A rats. FS-T, which has been found to suppress food intake mainly by activation of glucoreceptor neurons in the ventromedial hypothalamus, was injected intraperitoneally in a dose of 7 U/kg at 1930 hr, immediately before the dark period. Potency of FS-T in feeding suppression was much less in the obese rats than in their lean littermates or the Wistar King A rats. Meal size of the obese rats was decreased after the injection, but meal duration was unaffected. The suppressive effect on the lean rats and the Wistar King A rats included decrease of both size and duration of the meal. These results suggest that chemosensitivity in the ventromedial hypothalamus of Zucker obese rats may be impaired, which may be one explanation of the obesity in Zucker obese rats.     

Metabolic changes associated with obesity in adults

In order to find if the metabolic disorders more frequently found in our obese population were similar to the ones reported in the literature for other countries, a study was conducted in a group of 34 obese subjects (10 men and 24 women) whose only apparent alteration was a body mass index above 30 (mean value: 36.8 +/- 4.6) to obtain the relation between anthropometric measurements (Quetelet index, skinfold measures and waist/hip ratio) and plasma levels of nine biochemical parameters (including lipids, lipoproteins and glucose and insulin levels after an oral glucose load). The results revealed a tendency to the android distribution of fat in the female population, a significantly elevated triglyceride and total lipids levels and a decreased in HDL-cholesterol in both sexes. Hypercholesterolemia was present mainly in the male population. The most frequent dyslipidemia was Type IV (23%) followed by type IIb (15%). Practically none of the subjects had abnormal glycemic values after the glucose load, however the insulin levels were highly elevated in 80% of the patients, resulting in a great insulin/glucose ratios. Correlation analysis showed no association of the BMI with any biochemical parameter; only the insulin area was positively associated with anthropometric measures (mainly waist/hip ratio) and with the most altered biochemical parameter, the triglycerides. Variance analysis showed that only low HDL-cholesterol values were significantly different in patients presenting high blood pressure and familiar history of diabetes.     

Prostaglandin mediates endotoxaemia-induced hypophagia by activation of pro-opiomelanocortin and corticotrophin-releasing factor neurons in rats

Corticotrophin-releasing factor (CRF) and α-melanocyte-stimulating hormone (α-MSH), both of which are synthesized by hypothalamic neurons, play an essential role in the control of energy homeostasis. Neuroendocrine and behavioural responses induced by lipopolyssacharide (LPS) have been shown to involve prostaglandin-mediated pathways. This study investigated the effects of prostaglandin on CRF and α-MSH neuronal activities in LPS-induced anorexia. Male Wistar rats were pretreated with indomethacin (10 mg kg⁻¹; i.p .) or vehicle; 15 min later they received LPS (500 μg kg⁻¹; i.p .) or saline injection. Food intake, hormone responses and Fos–CRF and Fos–α-MSH immunoreactivity in the paraventricular and arcuate nuclei, respectively, were evaluated. In comparison with saline treatment, LPS administration induced lower food intake and increased plasma ACTH and corticosterone levels, as well as an increase in Fos–CRF and Fos–α-MSH double-labelled neurons in vehicle-pretreated rats. In contrast, indomethacin treatment partly reversed the hypophagic effect, blunted the hormonal increase and blocked the Fos–CRF and Fos–α-MSH hypothalamic double labelling increase in response to the LPS stimulus. These data demonstrate that the activation of pro-opiomelanocortin and CRF hypothalamic neurons following LPS administration is at least partly mediated by the prostaglandin pathway and is likely to be involved in the modulation of feeding behaviour during endotoxaemia.     

Increases in plasma glycerol levels precede the hypophagia following subcutaneous glycerol injection in rats

Cumulative food intake and plasma glycerol levels following subcutaneous glycerol injections were investigated in rats, because increases in plasma glycerol have been suspected to contribute to glycerol-induced hypophagia. Besides plasma glycerol, plasma non-esterified fatty acids (NEFA), plasma D-(-)-3-hydroxybutyrate (3-HB), blood glucose, and liver glycogen content were also measured. Two daily injections of 80 mg/kg body wt. glycerol did not affect food intake and failed to increase plasma glycerol 30 min after the injection. A single injection of 660 mg/kg body wt. glycerol reduced food intake and increased plasma glycerol 1-2 hours after the injection. This glycerol dose also increased liver glycogen content 1-2 hours after the injection but did not affect plasma NEFA and 3-HB. Rats injected with 660 mg/kg body wt. glycerol did not reduce feeding within the first 2 hours following the injection, when plasma glycerol levels were increased. Inhibition of feeding began at about 3 hours and continued up to 6 hours although plasma glycerol levels had declined to control values 5-6 hours after the injection. It is concluded that metabolic consequences of elevated plasma glycerol levels rather than increases in plasma glycerol levels per se elicit the food intake reduction following exogenous glycerol loads in rats.     

Anaphylactoid-inflammation-promoting factor. An insulin-induced factor derived from non-sensitized lymphocytes increases anaphylactoid inflammation in rats.

The experiments reported here indicate that, when exposed to insulin, viable lymphocytes rapidly released into the incubation medium a factor capable of increasing the dextran-induced anaphylactoid reaction, but having no effect on the inflammatory response evoked by 5-HT. This pro-inflammatory factor was shown to be elaborated by cell suspensions derived from lymph nodes of rats, rabbits, pigs or calves as well as from human tonsils. Thymus cells showed no such activity. The pro-inflammatory factor was termed as anaphylactoid-inflammation-promoting factor (AIPF). Its production depended upon the dose of insulin, and the time of exposure. AIPF was found to have an elution pattern in Sephadex G-100 gels similar to that of BSA (67,000 daltons). The activity was abolished by heat or incubation with DNase or a-chymotrypsin, but was not influenced by RNase. AIPF by itself did not induce increased vascular permeability, and proved to be distinct from the permeability factors present in the lysate of lymph node cells.     

Individual behavioral differences in recovery from abdominal sepsis in rats

Objective and Design:  In the present study we determined whether individual behavioral differences (high and low locomotor activity) differentially affected recovery from sepsis with high or low mortality. Methods:  Two trials were performed. Trial 1 with high mortality: Rats were randomly assigned to (1) control-A: anesthesia, (2) control-B: sham surgery, (3) sepsis: laparotomy and peritoneal contamination and infection (PCI) with human stool bacteria, (4) sepsis with antibiotic prophylaxis (cefuroxime/ metronidazole), and (5) sepsis with antibiotic plus G-CSF prophylaxis. Trial 2 with low mortality: Comparison of groups 3 and 5. Endpoints were mortality, behavior (open field and social interaction tests), and proinflammatory cytokines (interleukin-6 = IL-6 and macrophage inflammatory protein-2 = MIP-2). Results:  The combination of antibiotics plus G-CSF was most effective in reducing mortality in both trials and modified sickness behavior. Behavioral deficits were not statistically significantly improved by G-CSF. However, high versus low responders were differentially affected in both behavioral tests. Furthermore, IL-6 and MIP-2 were increased 24 hours after inoculum only in high responders with untreated sepsis and high mortality. Conclusion:  Improvement of sickness behavior in sepsis with G-CSF/antibiotic prophylaxis is a promising approach. The course of recovery from sepsis may depend on premorbid individual differences. Received 26 September 2008; returned for revision 25 October 2008; received from final revision 13 November 2008; accepted by M. J. Parnham 19 November 2008     

Metabolic effects of trekrezan during adaptation of rats to intermittent hypoxic hypoxia

The animals were adapted to intermittent hypoxic hypoxia in a flow pressure chamber for 3 days. Each one-day training session consisted of 4 elevations to an altitude of 6000 m for 20 min (15 m/sec, 20-min intervals between assents). Trekrezan (25 mg/kg intraperitoneally) was injected immediately after the end of daily training over 3 days. We showed that trekrezan increased the degree of adaptive metabolic changes in the brain, heart, and liver of rats during adaptation to hypoxic hypoxia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 53–56, January, 2008     

Cardiovascular concomitants of tactile and acoustic startle responses in spontaneously hypertensive and normotensive rats

In the present study we have simultaneously investigated cardiovascular and behavioral responses to repeated tactile and acoustic stimulation in adult, male, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Blood pressure and heart rate responses were increased in SHR vs. WKY rats following both types of stimuli. The pressor responses, but not the tachycardic responses, habituated with repeated stimulation in both strains and with both stimulus modalities. The rates of habituation were not significantly different between the two strains. Magnitudes of the behavioral startle responses were significantly elevated in SHR vs. WKY rats with tactile, but not with acoustic stimulation. No significant differences were found between the two strains with respect to the latency, with which the startle responses occurred. These data indicate that SHR as compared to WKY rats respond to repeated stimulation with two different stimulus modalities (tactile and acoustic) with significantly increased pressor and tachycardic responses. This cardiovascular hyperreactivity is not due to different degrees of habituation between the two strains and can be observed even in the absence of significant differences in standard behavioral startle response measures.     

Sleep and EEG spectra in rats recorded via telemetry during surgical recovery

STUDY OBJECTIVE: To determine sleep and EEG spectra in rats during surgical recovery. DESIGN: Sleep, activity, and EEG spectral power were examined in rats via telemetry on days 1, 2, 3, 7, 14, and 15 after implantation surgery. RESULTS: NREM sleep and total sleep were increased on days 1 and 2 compared to later days. REM sleep was decreased on days 2 and 3 compared to days 14 and 15, and activity was decreased on days 1 and 2 compared to later days. EEG power (0.5-5 Hz for NREM and wakefulness, and 5.5-10 Hz for REM and wakefulness) was increased on days 1-3 compared to days 7, 14, and 15. CONCLUSION: The results are discussed in terms of their implications for post-surgery stabilization of sleep and potential relevance for sleep after injury.