Centrally administered galanin inhibits osmotically stimulated arginine vasopressin release in conscious rats.

The effect of centrally administered galanin on arginine vasopressin (AVP) release was investigated in conscious rats. Intracerebroventricular injection of porcine galanin suppressed hypertonic saline-induced increase in plasma AVP in a dose-dependent manner (12.5-100 pmol/rat) at 10 min after the injection. Pretreatment with subcutaneous injection of naloxone (1 mg/100 g b.wt.) partially blocked the galanin-induced effect on plasma AVP. These results suggest that central galanin inhibits osmotically stimulated AVP release and endogenous opioids are, at least in part, involved in the mechanism.     

Antidipsogenic action of alpha-human atrial natriuretic polypeptide administered intracerebroventricularly in rats

Intracerebroventricular (i.c.v.) administration of alpha-human atrial natriuretic polypeptide (alpha-hANP) in a dose of 5 micrograms did not change water intake in normal rats, while 0.1 micrograms of angiotensin II (AII) and 0.5 micrograms of carbachol caused a marked increase in water intake for 30 min after i.c.v. injections. The water intake induced by 0.1 micrograms of AII was significantly suppressed by the simultaneous administration of 2 and 5 micrograms of alpha-hANP. However, alpha-hANP did not affect the water intake caused by 0.5 micrograms of carbachol. In 24-h water-deprived rats, alpha-hANP in doses of 2 and 5 micrograms pronouncedly inhibited the water intake. alpha-hANP did not change the food intake in 24-h fasted rats nor the locomotor activity in normal rats. These findings suggest that alpha-hANP in the central nervous system may play an important role in controlling drinking behavior, interacting with AII.     

The intracerebroventricularly administered mast cells degranulator compound 48/80 increases the pituitary-adrenocortical activity in rats

The effect of brain mast cells degranulation by compound 48/80 on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, and the involvement of a histaminergic mechanism in that stimulation was investigated in conscious rats. All the drugs were given intracerebroventricularly (icv), histamine antagonists 15 min prior to compound 48/80. Compound 48/80 induced a significant dose- and time-related increase in the serum corticosterone levels. That increase, measured 1 h after adminstration of compound 48/80, was moderately diminished by icv pretreatment of rats with mepyramine and cimetidine, histamine H₁- and H₂-receptor antagonists. Three hours after administration of compound 48/80 mast cells of the thalamus and the hypothalamus were completely degranulated. At the same time the thalamus and the whole brain histamine levels were substantially higher than in the saline-treated control rats.The above results suggest that histamine liberated from the brain mast cells and central histamine receptors play a moderate role in increasing the pituitary-adrenocortical activity by compound 48/80.The study was supported by the Polish Academy of Sciences, grant No. 06.03.     

Effects of intracerebroventricularly administered opioid peptide antagonists on tissue glycogen levels in rats after exercise

Background/aim Physical exercise is a state of physiological stress that requires adaptation of the organism to physical activity. Glycogen is an important and essential energy source for muscle contraction. Skeletal muscle and liver are two important glycogen stores, and the energy required to maintain exercise in rodents are provided by destruction of this glycogen depot. In this study, the effects of endogenous opioid peptide antagonism at the central nervous system level on tissue glycogen content after exhaustive exercise were investigated. Materials and methods Rats had intracerebroventricularly (icv) received nonspecific opioid peptide receptor antagonist, naloxone (50 μg/10 μL in saline) and δ-opioid receptor-selective antagonist naltrindole (50 μg/10 μL in saline) and then exercised till exhaustion. After exhaustion, skeletal muscle, heart, and liver were excised immediately. Results Both opioid peptide antagonists decreased glycogen levels in skeletal muscle. Although, in soleus muscle, this decrease was not statistically significant (p > 0.05), in gastrocnemius muscle, it was significant in the icv naloxone administered group compared with control (p < 0.05). Heart glycogen levels increased significantly in both naloxone and naltrindole groups compared to control and sham-operated groups (p < 0.05). Heart glycogen levels were higher in the naloxone group than naltrindole (p < 0.05). Liver glycogen levels were elevated significantly with icv naloxone administration compared with the control group (p < 0.05). Glycogen levels in the naloxone group was also significantly higher than the naltrindole group (p < 0.05). Conclusion Our findings indicate that icv administered opioid peptide antagonists may play a role in glycogen metabolism in peripheral tissues such as skeletal muscle, heart, and liver.     

Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats

Objective and design:Histamine is a potent stimulator of arginine vasopressin (AVP) release and therefore, the role of AVP was studied in the reversal of critical haemorrhagic hypotension induced by endogenous central histamine after inhibition of histamine N-methyltransferase (HNMT) activity in rats. Material:In 48 ethylurethane-anaesthetised male Wistar rats cardiovascular parameters and plasma hormone concentrations were measured. Treatment:Haemorrhage-shocked rats with mean arterial pressure (MAP) 20–25 mmHg were injected intracerebroventricularly (icv) with HNMT inhibitor metoprine (20 g) after pre-treatment with V_1a, V_1b and V₂ receptor antagonists – [-mercapto-,cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg⁸]AVP (10 g/kg; iv), SSR149415 (10 mg/kg; ip) and [adamantaneacetyl¹,O-Et-D-Tyr²,Val⁴, aminobutyryl⁶,Arg^8,9]AVP (10 g/kg; iv), respectively, or saline. Methods:MAP, heart rate (HR) and regional haemodynamics were monitored within 2 h after treatment or to death if it occurred earlier. Plasma hormone concentrations were measured using enzyme immunoassays. ANOVA followed by Neuman-Keules test, and Fishers exact test were used to compare the results. Results:Metoprine produced a long-lasting increase in MAP, HR, renal, hindquarters and mesenteric blood flows, and a 100% survival at 2 h (P < 0.05 vs. the control group). The action was associated with increased plasma AVP concentration (587.5 ± 98.9 vs. 387.3 ± 125.2 pg/ml; P < 0.05) in comparison to the control group as measured at 20 min after treatment. V_1a, but not V_1b and V₂, receptor antagonist inhibited metoprine-induced haemodynamic effects, with no influence on survival at 2 h. SSR149415 did not influence ACTH and adrenaline plasma concentrations in the metoprine-treated group. Conclusion:AVP, acting via V_1a receptors, is involved in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats.Received 9 October 2003; returned for revision 2 December 2003; accepted by A. Falus 23 December 2003     

Effects of intracerebroventricularly administered leptin on protein selection in the rat

The effect of centrally administered rat leptin on selection of 5 and 30% protein diets was investigated in male Sprague-Dawley rats with indwelling i.c.v. cannulas. Leptin (0 vs 2.5 microg/day) was administered for 4 consecutive days, followed by an 8-day withdrawal period. Total intake was reduced to approximately 50% of that in the vehicle injected group during each day following leptin administration. Intake of both the 5 and 30% diets was reduced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in leptin-treated rats was not different during the first day, but on Days 2-4, leptin-treated rats selected a 10% CP diet. Intake began to normalize within 24-48 h after the last treatment, and was not different by Day 3 of the withdrawal period. Body weight was reduced by leptin treatment, and despite the normalization of food intake, did not recover during the withdrawal period. Rats were sacrificed at the end of the 8-day withdrawal period. Despite the reduction in body and carcass weights, liver, kidney, heart, and soleus muscle weights were not different between control and leptin-treated groups when expressed on an absolute or relative basis. However, epididymal and retroperitoneal fat pad weights were still reduced 56 and 78%, respectively, in rats that had been previously treated with leptin for 4 days and then not treated for 8 days. In addition, circulating T3 levels remained elevated in rats that had been treated with leptin. Centrally administered leptin has little effect on muscle mass, but had potent effects on intake of nonobese rats and a sustained effect on adipose tissue mass, thyroid hormone status, and body weight after withdrawal. Results from rats selecting between diets varying in protein content suggest that leptin may cause avoidance of protein.     

Involvement of central noradrenergic system in the pressor effect of histamine administered intracerebroventricularly in rats - haemodynamic studies

Inflammation Research -     

Central histamine-induced reversal of critical haemorrhagic hypotension in rats – a comparison with the pressor effect of arginine vasopressin

Inflammation Research -     

Hemodynamic effects of moderate increase of the plasma vasopressin level in conscious dogs

Summary The influence of moderate increase of the plasma ADH level on aortic and central venous pressures, heart rate, cardiac output, stroke volume, central blood volume, systemic peripheral resistance and plasma volume was examined in conscious dogs. The animals were given 0.75 mU ADH/kg b.w. in single intravenous injection as a priming dose. This was followed by a constant infusion of the hormone at a rate of 0,12 mU/min/kg/0.2 ml 0.9% NaCl solution lasting one hour. Plasma ADH level measured at 30 min of the infusion was equal to 22 ± 4 U/ml. A significant increase of aortic (mean systolic and diastolic) and central venous pressures, systemic peripheral resistance and of plasma volume was observed in the course of the infusion. It was accompanied by a decrease of heart rate, cardiac output and central blood volume. Changes of stroke volume were not significant.As the plasma level produced by the infusion was such as that following a moderate nonhypotensive haemorrhage [30], the rôle of the hemodynamic effects of vasopressin in maintenance of the blood pressure and volume in hypovolemia is discussed.     

In vivo dynamics and distribution of intracerebroventricularly administered gadodiamide, visualized by magnetic resonance imaging

Direct injections into the cerebroventricles have been extensively utilized in neurophysiological studies. Mapping the distribution of injectate after intracerebroventricular injection has been made only by post mortem analysis, and the dynamic distribution of injectate within the brain has not been well characterized. In this report, we apply contrast-enhanced magnetic resonance imaging to study the pharmacokinetics and extent of non-ionic gadodiamide transport into brain tissue in vivo after intracerebroventricular administration. The results indicate that intracerebroventricular injectate travels quickly throughout the ventricular system from the lateral ventricular site of injection to the fourth ventricle and foramina of Luschka and Magendie within 2 min. After this, the signal intensity begins to increase in the periventricular and paraventricular brain parenchyma. Contrast enhancement is visible 2 mm into the brain tissue from the ventricles. Quantitative analysis of the data shows that the transport of gadodiamide across the ependymal layer that lines the cerebrospinal fluid space characterized a rate constant of 0.066+/-0.017 min(-1). These results provide a better understanding of chemical transport and diffusion following direct injection into the cerebroventricles. They provide information on the in vivo dynamics of injectate after intracerebroventricular administration, and show that contrast enhanced magnetic resonance imaging may be used to more precisely define the target sites of chemicals after intracerebroventricular administration into the brain.     

orexin A和orexin 1型受体在新生大鼠与成年大鼠延髓分布的比较

本文研究orexinA(OXA)和orexin 1型受体(OX1R)在新生大鼠与成年大鼠延髓的分布及比较。新生(1～5d)和成年(6～8周)SD大鼠,取其延髓,采用免疫组织化学方法和图像分析技术,观察OXA和OX1R在新生与成年SD大鼠延髓的分布。结果显示,OXA免疫反应阳性纤维和OX1R免疫反应阳性细胞在新生和成年SD大鼠延髓内有广泛分布,主要分布在延髓腹外侧区(ventrolateralmedulla,VLM)和舌下神经核(hypoglossalnucleus,XII)。在这两个区域,新生大鼠组的OX1R免疫反应阳性细胞的相对光密度值均低于成年大鼠组(P<0.001)。结果表明随着大鼠发育成熟,OX1R表达水平增加,可能与其生理功能完善有关。OXA免疫反应纤维和OX1R免疫反应阳性细胞在延髓的VLM和XII的表达提示可能与心血管和呼吸等活动的调节有关。     

Levels of plasma and aortic lipids in young exercised rats with a diminished weight gain

Summary Young exercised rats with a diminished weight gain had a decrease in high density lipoprotein (HDL) cholesterol and phospholipid levels in the plasma and augmented free cholesterol and phosphatide in the aorta. When the weight gain in the trained rats paralleled the gain in non-exercised animals, the values of these lipids were not altered. The levels of aortic free cholesterol in the non-exercised and exercised groups were inversely associated with concentrations of HDL-cholesterol, but were not related to the activities of lecithin cholesterol acyltransferase. In addition, the total cholesterol and phospholipid contents in the aorta negatively correlated with HDL-cholesterol concentrations. We propose that in young exercised rats with a diminished weight gain, the removal of aortic lipids is hampered due to a reduction in HDL-cholesterol.     

Effect of treadmill running and swimming on plasma and brain vasopressin levels in rats

Summary The influence of treadmill or swimming exercise on resting values of plasma and brain arginine vasopressin (AVP), and plasma sodium, potassium, osmolality and proteins was studied after 5 weeks of training using female Wistar rats. The duration of daily training sessions was progressively increased to reach 6 h/ day for swim training (S) and 3 h/day for treadmill running (T). Compared to their untrained controls, treadmill and swim training were respectively associated with: 1. a significant lower body weight; 2. a decreased plasma AVP (36.4% for T and 47.4% for S) and hypothalamic AVP (20% for T and 16% for S); 3. a higher hypophyseal AVP (145% for T and 36.3 for S); 4. a decreased plasma osmolality (6.7% for T and 6.1% for S), sodium (1.2% for both) and potassium. (15% for T and 22.4% for S); and 5. no change in protein concentration. For T, rectal temperature increased (38.5±0.20 to 39.7±0.5) and for S rectal temperature decreased from 38.6±0.12 to 37.74±0.10).The differences observed in AVP contents of the pineal and Harderian glands (enhanced only in the treadmill groups) could be explained by the supposed role of these glands in thermoregulation. Two conclusions could be drawn from this study: 1. there are no parallel changes in the hypotrtalamo-hypophyseal system (where AVP plays its endocrine role) and the brain (where AVP is a neurotransmitter); 2. plasma changes could be explained by an extracellular fluid expansion with Na and K loss leading to a decrease in AVP secretion.     

Potentiation of vasopressin secretion by footshocks in rats

Effects of footshocks (FS) on antidiuretic hormone (vasopressin, VP) in the plasma were studied in rats. Continuously applied FS of 60 s period with 5 ms pulses at 50 Hz frequency significantly increased VP as well as adrenocorticotrophic hormone (ACTH) in the plasma in a time- and shock intensity-dependent manner. Contrarily, the 50 Hz FS of 2 s period as repeated intermittently at every 15 s for over the period of 2, 10, and 30 min were much less effective for increasing plasma VP, whereas these intermittent FS increased plasma ACTH to an extremely high level. During the inter-shock intervals of 13 s between successive two shock periods rats exhibited a "freezing" behavior. Hypertonic saline or urethane injected I.P. immediately after termination of the intermittent FS significantly increased VP as well as ACTH in the plasma. These data clearly indicate that FS potentiate VP secretion and suggest the possibility that emotional stress may suppress the noxious stimuli-induced VP secretion.     

Masculinization diminished by disruption of prenatal estrogen biosynthesis in male rats

Male rats were exposed to the aromatization inhibitor 1,4,6-androstatriene-3, 17-dione (ATD) in utero via prenatal injections to the mother on days 10 through 22 of gestation. At birth anogenital distance (AGD) and body weight (BW) were measured to assess effects of ATD on the development of genital morphology and body weight. Animals were castrated in adulthood and tested for the display of masculine sexual behavior in response to daily injections of 100 μg testosterone propionate replacement therapy. Prenatal exposure to ATD resulted in males with significantly decreased copulatory rates (MIPM) and slightly diminished probabilities of ejaculating when compared to control animals. Overall mounting, and intromission frequencies as well as percentages of animals displaying mounts and intromissions did not differ significantly across groups. These data lend support to the idea of a prenatal androgen-sensitive phase of neural sexual differentiation in which masculinization occurs, and further suggests that androgen aromatized to estrogen may be important for masculinization prenatally.     

Reduction of carrageenan- bradykinin- and histamine-induced acute inflammation by experimental eosinophilia in rats.

An examination was made of the effects of eosinophilia on acute inflammation. Sprague Dawley rats were infected with Trichinella spiralis larvae which resulted in a blood eosinophilia. Groups of rats with the induced eosinophilia, and untreated rats without the eosinophilia, were treated with carrageenan, bradykinin or histamine in the hind paw to induce local inflammation. Paw oedema induced by carrageenan as a measure of the inflammation was much reduced in those rats with an eosinophilia, and slightly but significantly reduced in the site treated with histamine or bradykinin. Though other anti-inflammatory factors may have participated, it is believed that the reduction in inflammation was due to the eosinophils. Pretreatment of the rat paws with an eosinophil chemotactic factor tetrapeptide (ECF-A) caused no chemotaxis and therefore no effect on histamine-induced oedema.     

Attenuation of stress-induced elevations in plasma ACTH level and body temperature in rats by green odor

To investigate the effect of green odor on the elevation of the plasma adrenocorticotropic hormone (ACTH) levels and body temperature (T(b)) induced by stress, adult male rats were subjected to a 2-h immobilization stress and exposed to green odor or its vehicle only. In comparison with the vehicle group, animals in the green odor group showed a significant reduction in plasma ACTH levels at the end of the stress when green odor was applied during the stress. The elevated plasma ACTH levels 2 days after the stress were reduced by green odor applied 0, 1, 2, 4 or 6 h after the beginning of the stress. Neither the immediate nor the long-lasting plasma ACTH response was affected by a prestress treatment of green odor. T(b) elevation was evident following the end of the stress and during the light phase the day after the stress. Both the immediate and the long-lasting elevations in T(b) were attenuated by green odor. These data suggest that green odor extracted from green leaves has a relieving effect on plasma ACTH and T(b) levels induced by an immobilization stress for not only immediate but also long-lasting periods.     

出生前尼古丁暴露增加新生大鼠下丘脑orexin A及延髓内orexin 1型受体表达

流行病学调查显示,出生前暴露于烟雾环境是新生儿猝死综合征发生的首位原因,尼古丁是香烟烟雾中最主要的影响胎儿神经系统发育的成分。为了观察出生前尼古丁暴露对新生大鼠下丘脑orexin A(OXA)及延髓内orexin 1型受体(OX1R)表达的影响,本实验将20只雌性成年大鼠随机均分为二组,怀孕后第5 d开始每天分别皮下注射尼古丁6 mg/kg(模型组)或等量的生理盐水(对照组),直至分娩。随机选取模型组和对照组所产的新生大鼠(1～3 d),采用免疫组织化学方法和图像分析技术,观察新生鼠下丘脑内OXA及延髓内OX1R阳性神经元的分布情况。结果显示:两组新生大鼠下丘脑内OXA免疫阳性细胞均有表达,且都主要存在于下丘脑背内侧区与穹窿周围,模型组的新生大鼠OXA免疫阳性细胞的相对光密度(ROD)值高于对照组(P<0.05)。延髓内OX1R免疫阳性细胞在两组内均有广泛分布,主要分布在腹外侧区和舌下神经核。在这两个区域,模型组新生鼠的OX1R免疫阳性细胞的ROD值均高于对照组(P<0.001)。以上结果表明,出生前尼古丁暴露的新生大鼠,下丘脑OXA及延髓内OX1R的表达均上调,提示出生前尼古丁暴露改变了新生大鼠脑内OXA系统递质的释放和突触传递,这意味着脑内orexin系统参与出生前尼古丁暴露导致的各种疾患。