Anabolic androgenic steroids affects alcohol intake, defensive behaviors and brain opioid peptides in the rat

The present study investigated whether a relationship exists between nandrolone decanoate and voluntary ethanol intake in laboratory rats. Animals were subjected to daily subcutaneous injections with nandrolone decanoate (15 mg/kg) during 2 weeks. One group of animals was tested for voluntary alcohol intake 1 week after the end of the 2-week treatment period and another group received alcohol 3 weeks after the treatment. In addition, assessment of defensive behaviors and immunoreactivity (ir) levels of the brain opioid peptides dynorphin B and Met-enkephalin-Arg-Phe (MEAP) were performed. The nandrolone decanoate-treated animals were significantly more aggressive and showed lower fleeing and freeezing reaction than the oil-treated controls. Treatment with nandrolone decanoate enhanced voluntary alcohol intake, regardless if it was presented 1 or 3 weeks after end of the treatment period. These animals had a decreased activity of dynorphin B-ir in the nucleus accumbens, decreased levels of MEAP-ir in the periaqueductal gray (PAG) and higher levels of MEAP-ir in the hypothalamus compared to controls. In line with previous studies, this suggests that the altered dynorphin B-ir activity may promote the rewarding effects of ethanol and thereby increasing alcohol intake, whereas MEAP-ir may be associated with the ability to control the aggressive reaction. Abuse of nandrolone decanoate may thus constitute a risk factor for increased alcohol consumption and defensive aggression. In human, this constellation of behavioral symptoms is closely related to acts of crimes and violence and is often observed among those abusing anabolic androgenic steroids.     

Oral quinine pharmacokinetics and dietary salt intake

OBJECTIVES: The objective was to determine whether or not dietary salt intake affects the relative bioavailability of oral quinine. Salt intake has been shown to alter quinidine bioavailability. METHODS: The pharmacokinetic properties of oral quinine sulphate (600 mg salt) were investigated in seven healthy Caucasian volunteers, in a randomised, crossover study, on low- and high-salt diets. Plasma quinine concentrations were measured by high-performance liquid chromatography (HPLC) and the 24-h urinary sodium excretion was assayed. RESULTS: Although the 24-h urine sodium excretion was significantly higher when the volunteers were on a high-salt diet, there were no significant differences in quinine AUC0-infinity, tmax, and Cmax after the two diets. The median (range) quinine elimination half-life was significantly shorter after a high-salt diet [8.5 (4.3-10.2) h] than after a low-salt diet [10.0 (7.6-14.8) h] (P = 0.04). CONCLUSION: Dietary salt does not affect the relative oral bioavailability of quinine sulphate.     

Protection of methionine in peptides during iodination by sulfonium salt formation

A method for the prevention of methionine oxidation during iodination of tyrosine containing peptides is reported. The methionine containing peptide is converted into the corresponding S-tert.-butylsulfonium derivative, which is iodinated using iodine monochloride. After removal of the S-tert.-butyl group and purification, sulfoxide-free 3,5 diiodotyrosine (Dit) peptides were obtained. Dit⁸-substance P, Dit⁸-physalaemin^6–11 and Dit¹, Met⁵-enkephalin were synthesized by this route. Tritium labeling of Dit¹, Met⁵-enkephalin yielded ³H-enkephalin with a specific radioactivity of 38 Ci/mmol.     

Dietary salt intake and the clonidine suppression test

We studied the effects of one week of dietary salt restriction and one week of salt loading on hemodynamic and plasma catecholamine responses to clonidine. Among 11 outpatients with essential hypertension, urinary sodium excretion averaged 29 mEq/d during salt restriction and 322 mEq/d during salt loading. Among eight inpatient normotensive subjects, urinary sodium excretion averaged 11 mEq/d during salt restriction and 300 mEq/d during salt loading. Three hours after administration of oral clonidine 300 micrograms, the hypertensive patients had an average (+/- one standard deviation) decrease in mean arterial pressure of 20 +/- 6% while receiving the low salt diet and 19 +/- 9% while taking the high salt diet, with decreases in venous plasma norepinephrine (NE) of 61 +/- 15% and 61 +/- 16%, respectively. The normotensive subjects had a decrease in mean arterial pressure of 16 +/- 8% with the low salt diet and 15 +/- 9% with the high salt diet, with decreases in venous plasma NE of 64 +/- 10% and 66 +/- 8%. Thus, in neither group were the percent decreases in plasma NE or in mean arterial pressure after clonidine affected by diet. Short-term, large-magnitude changes in dietary intake of sodium do not affect the sympathetic contribution to blood pressure as indicated by percent responses of plasma NE or of mean arterial pressure to clonidine administration.     

Cerebrovascular and renal effects of cerebrolysin and dependence on salt intake

Experiments on rats with occluded common carotid arteries showed that an excess sodium chloride consumption increased the loss of test animals as a result of the maximum decrease in the local cerebral blood flow and sharply pronounced brain swelling. The sodium chloride substitute hyposol (giposol) reduced the extent of cerebral ischemia and brain swelling effect and increased the renal perfusion and diuresis levels. In the test animals receiving a high-Na diet, the efficacy of cerebrolysine was less pronounced. In contrast, hyposol increased the antiischemic, saluretic and antiswelling effects of cerebrolysine under the carotid artery occlusion.     

Effect of capsaicin neonatal treatment on the salt intake of the adult rat.

The present study investigated the involvement of capsaicin-sensitive sensory neurons on salt intake control in the rat, following capsaicin neonatal treatment. Capsaicin did not affect salt appetite induced by intramuscular injection of deoxycorticosterone enantate, or by intracranial injection of renin. Moreover, it did not alter salt preference of rats given access to a variety of NaCl concentrations, or the need-free salt intake of multidepleted male rats. On the other hand, in response to furosemide-induced sodium depletion, the salt intake of capsaicin-treated rats was lower than that of controls. However, furosemide-induced Na+ excretion of capsaicin-treated rats proved to be lower than that of controls, thus suggesting that difference in salt intake might be secondary to lower sensitivity of capsaicin-treated rats to the natriuretic action of furosemide. Salt intake is known to be influenced by sensory information from the oral cavity, from the liver and from the intravascular compartment. The absence of effect of capsaicin neonatal treatment suggests that sensory fibers relevant to salt intake control may not be capsaicin sensitive. On the other hand, our findings indicate that capsaicin treatment alters the renal response to furosemide and stimulate further studies on the effects of capsaicin on renal function.     

Sedation and need-free salt intake in rats treated with clonidine

The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need-free 1.5% NaCl intake and on performance (defined as percent of a complete trial) in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18 and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did not alter the performance in the rotarod test. The dose of 36 microg/kg did not inhibit 10% sucrose intake. Only the highest dose (72 microg/kg) of clonidine inhibited the 1.5% NaCl intake and the performance in the rotarod test, and produced signs of sedation. Sedation was determined either by change in posture (immobility or lack of postural tonus) of the animals during the ingestive test or by their performance in the rotarod test. The results suggest that sedation is not a determinant effect on the inhibition of 1.5% NaCl intake induced by clonidine.     

Endocrine control of ethanol intake by rats or hamsters: Relative contributions of the ovaries,adrenals and steroids

Alcohol intake and preference by female rats decreases during pregnancy or following ovariectomy (OVX) in accordance with a model derived from the saccharine preference literature. However, the present Experiment 1 revealed that ovariectomized rats only modestly increased 4% ethanol preference following subcutaneous implantation of Silastic implants containing estradiol. In Experiment 2, OVX female hamsters actually had greater alcohol preference compared to controls. This information led to the suggestion that ovarian estradiol in rats might be effecting alcohol intake by influencing adrenal corticosteroid release, something that does not occur in female hamsters. Adrenal glucocorticoids are known to profoundly alter sensitivity to taste, olfactory and auditory stimuli. Therefore, groups of rats were sham operated, OVX, adrenalectomized (ADX) or both OVX and ADX to test for the relative endocrine effects on alcohol preference. The rank ordering of preference deficits produced was SH < OVX < ADX < OV-ADX. Reductions in alcohol preference relative to the SH group were about 34% 58% and 75% for the OVX, ADX, and OV-ADX groups, respectively. Daily corticosterone injections increased alcohol preference of the ADX and OVX groups, but not of the OV-ADX animals. The results support the hypothesis of adrenal-ovarian interactive control of ethanol intake, but provide no satisfactory explanation for the diminished alcohol preference during pregnancy.     

Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

1. Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) - cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR). 2. Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3. In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY. 4. In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake. 5. Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake. 6. These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.     

Neural-renal interactions in the hypertension induced by papillary necrosis: role of dietary salt intake

The effects of high salt intake (1.0% NaCl in the drinking water) on rats made hypertensive by 2-bromoethylamine hydrobromide (BEA) treatment (200 mg/kg, i.p.) were examined. BEA-induced medullary necrosis resulted in a mild hypertension (146 +/- 5 mm Hg) that was exacerbated by 4 weeks of high salt intake (163 +/- 6 mmHg). BEA-treated rats had significant salt-induced increases in urinary norepinephrine excretion and hypothalamic and brainstem norepinephrine content, that were not present in BEA-treated rats drinking tap water or control rats drinking saline. BEA treatment in combination with increased salt intake produced a decrease (p less than 0.05) in renal dopamine content and adrenal norepinephrine stores relative to BEA treatment alone. BEA treatment also significantly decreased renal norepinephrine stores and dopamine binding sites irrespective of salt intake. Renal alpha 2-adrenergic receptors and central nervous system stores of dopamine and serotonin were unaffected by BEA treatment. Renal function was well preserved as indicated by normal creatinine, glucose and protein excretion; however, significant (p less than 0.05) disruption of the urinary concentrating mechanism was present. These studies suggest that BEA-induced hypertension has a neural component that is exacerbated by high salt intake. The primary defect in BEA hypertension appears to be the lack of circulating antihypertensive lipids that attenuate the ability of salt loads to simulate sympathetic nervous system activity.     

重症颅脑损伤后脑性盐耗综合征的诊治策略

目的 探讨重型颅脑损伤患者并发脑性盐耗综合征的病因、发病机制、诊断及治疗经验.方法 回顾性分析重型颅脑损伤后发生脑性盐耗损综合征的22例患者,通过其临床表现及实验室检查明确诊断.确定有效的治疗方法.结果 除2例死于继发性疾病外,20例患者低血钠症状恢复.结果 低血钠、高尿钠、低血容量及意识状态改变是脑性盐耗综合征的诊断依据,水化和补盐治疗安全有效.