Effects of L-arginine and SIN-1 on sleep and waking in the rat during both phases of the light-dark cycle

The effects L-arginine (0.15-0.60 micromol), a nitric oxide precursor, and SIN-1 (3-morpholino-sydnonimine; linsidomine) (0.05-0.2 micromol), a nitric oxide donor, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. L-arginine or SIN-1 given intracerebroventricularly during the light phase of the light-dark cycle induced no significant changes in sleep variables. On the other hand, administration of L-arginine or SIN-1 during the dark phase significantly increased slow wave sleep and reduced waking during the first 4 h of the recording period. The time spent in rapid-eye-movement sleep (REMS) was not significantly modified. The increase of slow wave sleep and/or reduction of waking was already evident during the first 2 h of recording. On the other hand, values of these variables were not different from control values during post-injection hours 5 and 6. Our findings confirm the role of nitric oxide, generated from L-arginine or released from SIN-1, in the regulation of sleep variables in the rat.     

Effect of opioid peptides on regional hemodynamics in waking rats

The hemodynamic effects of intravenously administered relatively selective mu-(DAGO) and delta-(DADL) opioid agonists were investigated in conscious rats. The radioactive microsphere technique was used to measure regional blood flow in 10 zones before and 5 min after bolus injection of each peptide. Both opioid agonists in a dose of 1 mumol/kg produced transient hypotension, bradycardia and apnoea. DADL injection increased blood flow in the adrenals and decreased it in the muscles; vascular resistance spleen. DAGO administration increased blood flow in the adrenals and decreased it in the pancreas and skin, whereas vascular resistance increased in the pancreas and skin and decreased in the adrenals. Naloxone pretreatment diminished regional blood flow responses to DAGO. Regional hemodynamic changes after peptide administration are suggested to be connected with the activation of peripheral opiate receptors. High differentiation of regional vascular responses may be related to heterogeneous distribution of mu- and delta-opiate receptors in the body.     

Effects of interactions between various fats and active/passive phases on postprandial inflammation in rats

The circadian clock controls number of behavioral and physiological processes during daily light/dark cycle including inflammation and vascular injury. However, how reciprocal interaction of dietary fats and light/dark cycle affects postprandial inflammation is currently unknown. To this end, effects of various dietary fats given to rats by gavaging either in light or dark phase on postprandial inflammation were compared. Sunflower oil load activated greater number of inflammatory CD markers in passive phase whereas the butter load in active phase compared to their counter phase. The inflammatory influence of fish oil load appeared to be mostly confined to passive phase. Differences found between the levels of some of the inflammatory markers in active and passive phases of normal fed rats were altered by fat/oil administrations. We conclude that influences of dietary fats/oils on postprandial inflammatory changes might depend not only on their fatty acid compositions but also on their ingestion times.     

Effects of reciprocal interactions between various dietary fats and circadian phases on postprandial hyperlipidemia in rats

Expression levels of various intestinal proteins involved in postprandial lipoprotein assembly as well as plasma triglyceride concentration exhibit daily oscillations indicating circadian control. The length of the carbon chain and degree and position of unsaturation of fatty acids influence triglyceride secretion by the enterocytes. To this end, effects of reciprocal interactions of various single fats/oil (olive oil, fish oil or butter) gavaging either in active or passive phase were investigated in rats. Fat/oil gavaged in the active phase of circadian rhythm resulted in higher postprandial serum triglyceride levels compared to that in the passive phase. Moreover, olive oil led to higher MTP activity and apo B-48 gene expression, while fish oil gavaging caused more prominent apo B-48 and MTP gene expression when they were given in the passive phase. The present results indicate that circadian time at which fat or oil gavaged once might exert influence on postprandial lipoprotein synthesis/assembly.     

Effect of lithium preparations on cardiac arrhythmias due to strophanthin in waking rats

It was shown in experiments on conscious rats that intravenous injection of strophanthine in toxic doses provokes heart arrhythmias and death of the animals. Lithium drugs (lithium chloride and lithium hydroxybutyrate) injected during arrhythmias led to a short-lived effect of heart rhythm normalization. Lithium hydroxybutyrate was more effective if administered shortly after strophanthine injection, reducing the latter's cardiotoxic effect and preventing the death of the majority of the animals.     

Effects of consecutive high-dose alcohol administration on the utilization of sulfur-containing amino acids by rats

In this study, we attempted to evaluate changes in sulfur-containing amino acid (SCAA) metabolism after short-term high-dose alcohol ingestion. At the beginning of the study, six animals were sacrificed as the baseline group and then other animals in the experiment were consecutively gavaged with alcohol (30%, 3 g/kg) for 7 days. Animals (n=6 each) were subsequently sacrificed at the time points of Days 1 (Group E1), 3 (Group E3) and 7 (Group E7). Blood samples and selected tissues were collected at each time interval. SCAA, pyridoxal phosphate (PLP) and glutathione (GSH) levels were analyzed. Results showed that taurine levels of tissues (brain, liver, heart and kidneys) all declined after the ethanol intervention and continued to decrease in selected tissues except the brain during the experiment. Furthermore, the trends of plasma taurine and PLP contents were highly correlated (r=.98, P=.045). A similar utilization pattern of plasma taurine and PLP indicated that transsulfuration preferred taurine production to GSH synthesis. The trend of plasma taurine levels being positively correlated with PLP levels reveals that dramatic transsulfuration occurred to meet the urgent demand for taurine by brain cells. In conclusion, we reported that continual alcohol ingestion alters SCAA utilization, especially by depletion of taurine and hypotaurine and by elevation of S-adenosyl homocysteine in the selected organs.     

The hemodynamic and metabolic effects of 2-deoxy-D-glucose in waking Wistar rats]

The effect of 2-deoxy-D-glucose (2-DG) in a dose of 250 mg/kg as a stressogenic factor on changes in hemodynamic parameters and metabolism in awake rats was quantified during 6 hours. It was found that a single 2-DG injection causes lowering of blood pressure on min 40 and 120. Heart rate tended to slow down. Diminished glucose concentration in the brain observed on experiment minute 15 induced a number of adaptive reactions in the body. Epinephrine plasma levels increased sharply on min 15 and 40. Norepinephrine concentrations elevated slightly only at the beginning of the experiment. The maximal glucose level in blood plasma was observed on min 40 and 120 and that of lactate 40 min following 2-DG injection. The level of immunoreactive insulin rose. Glucose content in the heart came up sharply on min 15 and 40. Lactate concentration in the heart increased continuously.     

Cardiopulmonary control in sleeping Sprague-Dawley rats treated with hydralazine

Carley, David W., Sinisa M. Trbovic, Alex Bozanich, andMiodrag Radulovacki. Cardiopulmonary control in sleepingSprague-Dawley rats treated with hydralazine. J. Appl.Physiol. 83(6): 1954-1961, 1997.To test thehypothesis that hydralazine can suppress spontaneous sleep-relatedcentral apnea, respiratory pattern, blood pressure, and heart periodwere monitored in Sprague-Dawley rats. In random order and on separatedays, rats were recorded after intraperitoneal injection of1) saline or2) 2 mg/kg hydralazine. Normalizedminute ventilation(NI)declined significantly with transitions from wake tonon-rapid-eye-movement (NREM) sleep (5.1%;P = 0.01) and rapid-eye-movement (REM)sleep (4.2%; P = 0.022).Hydralazine stimulated respiration(NIincreased by 21%; P < 0.03) andeliminated the effect of state onNI. Bloodpressure decreased by 17% after hydralazine, and the correlationbetween fluctuations in mean blood pressure andNI changedfrom strongly positive during control recordings to weakly negativeafter hydralazine (P < 0.0001 foreach). Postsigh and spontaneous apneas were reduced during NREM and REMsleep after hydralazine (P < 0.05 for each). This suppression was strongly correlated with the reductionin blood pressure and with the degree of respiratory stimulation. Weconclude that mild hydralazine-induced hypotension leads to respiratory stimulation and apnea suppression.