Chronobiological parameters of pain sensitivity of rats and mice

Circadian and 12-hour rhythms of pain sensitivity to stimuli of different origin were detected in male rats and mice by cosinor analysis in chronobiological experiments. The minimal pain sensitivity to thermal and electric stimulation was observed in rats during the first half of the light phase of 24 h, while in the case of mechanical stimulation it was observed during the dark phase. Biorhythms of sensitivity of mice and rats to thermal pain exposure were similar. Hence, the chronobiological organization of pain sensitivity depends mainly on the type of nociceptive stimulation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5, pp. 537–540, May, 1995     

Anti-inflammatory effect of Mentha longifolia in lipopolysaccharide-stimulated macrophages: Reduction of nitric oxide production through inhibition of inducible nitric oxide synthase

Abstract

Mentha longifolia is an aromatic plant used in flavoring and preserving foods and as an anti-inflammatory folk medicine remedy. The present study assessed the effects of M. longifolia extracts, including essential oil and crude methanol extract and its fractions (ethyl acetate, butanol and hexane), on nitric oxide (NO) production and inducible NO synthase (iNOS) mRNA expression in lipopolysaccharide (LPS)-stimulated J774A.1 cells using real-time polymerase chain reaction (PCR). The cytotoxic effects of the extracts on the cells were examined and non-cytotoxic concentrations (<0.2?mg/ml) were used to examine their effects on NO production and iNOS mRNA expression. Only the hexane fraction that contained high levels of phenolic and flavonoid compounds at concentrations from 0.05–0.20?mg/ml significantly reduced NO production in LPS-stimulated cells (p?<?0.001). Real-time PCR analysis indicated the ability of this fraction at the same concentrations to significantly decrease iNOS as well as TNFα mRNA expression in the cells (p?<?0.001). All extracts were able to scavenge NO radicals in a concentration-dependent manner. At concentrations greater than 0.2?mg/ml, total radicals were 100% scavenged. In conclusion, M. longifolia possibly reduces NO secretion in macrophages by scavenging NO and inhibiting iNOS mRNA expression, and also decreases TNFα pro-inflammatory cytokine expression, thus showing its usefulness in the inflammatory disease process.     

In Vivo Accumulation of nitric oxide in blood vessels

Against the background of NO-synthase blockade, diethyldithiocarbamate had no effect on the tone of isolated rat aorta, but induced relaxation of aorta preparations isolated afterin vivo NO accumulation and isolated aorta incubated with dinitrosyl iron complex. Guanylate cyclase inhibitor methylene blue prevented the relaxation induced by diethyldithiocarbamate. These data suggest that accumulation of NO in the organism can result in its accumulation in the vessel wall. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 629–632, June, 1999     

Role of nitric oxide in anaphylactic shock

Nitric oxide, synthesized from the guanidino group ofl-arginine by nitric oxide synthase, has an important role in pathophysiological changes associated with anaphylaxis. Nitric oxide production due to activation of constitutive nitric oxide synthase is detected using a nitric oxide-selective electrode in anaphylactic rabbitsin vivo. A nitric oxide synthase inhibitor attenuates hypotension and hemoconcentration and decreases venous return but does not improve cardiac depression. Nitric oxide functionally antagonizes the effects of vasoconstrictors released by anaphylaxisin vitro. In animals pretreated with a nitric oxide synthase inhibitor, the cardiac output falls significantly, although venous return is increased. Pulmonary resistance is significantly increased with a nitric oxide synthase inhibitor, andl-arginine attenuates the bronchospasm. These findings suggest that production of nitric oxide may reduce the pathophysiologic changes, except for vasodilatation, associated with anaphylaxis.     

Endothelial function and nitric oxide production in rats adapted to intermittent hypoxia

Adaptation to intermittent hypoxic hypoxia did not affect the endothelium-dependent relaxation of the aorta in rats, but significantly increased the relaxation of their tail artery. Following the adaptation, the NO level fell in the liver, intestine, and kidneys and remained unchanged in the spleen. Adaptation to hypoxia presumably limits NO synthesis and/or release in the vascular endothelium or enhances the capacity of this oxide to bind in a physiologically active depot. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 11, pp. 495–498, November, 1995 Presented by Yu. A. Vladimirov, Member of the Russian Academy of Medical Sciences     

Is nitric oxide involved in the adaptation to the stress-induced damage?

The iron dinitrosyl complex (a NO donor), adaptation to stress, and their combination suppress the stress-induced ulcer formation. Nω-nitro-L-arginine, a NO synthetase inhibitor, reduce the antistress effect of adaptation. Severe stress induces a sharp decrease in the NO production in the liver and brain. After adaptation to stress, the NO production in the liver and brain does not differ significantly from control levels. However, adaptation attenuates a decrease in the NO production in the liver caused by severe stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 274–277, September, 1998     

Enhanced production of nitric oxide in rat organs in heat shock

Heat shock is shown to lend a marked boost to the production of nitric oxide (NO), which attains the maximal level 1 hour after exposure and returns to the initial level after 24 hours. The generation of NO in all studied organs is completely blocked by Nω-nitro-L-arginine, an inhibitor of NO synthase, both in the control and after hyperthermia. Thus, heat shock markedly stimulates NO synthesis. This generalized effect may underlie the drop in the peripheral vascular tone that is characteristic of heat shock. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 520–523, May, 1996     

Nitric oxide synthase in bronchial epithelium and nitric oxide metabolites in the lungs of rats with bronchial asthma after fenoterol inhalation

Nitric oxide synthase of the bronchial epithelium and concentrations of nitric oxide metabolites (NO₂ ⁻ and NO₃ ⁻) in bronchoalveolar lavage fluids were measured in rats with bronchial asthma after fenoterol inhalation. It was suggested that nitric oxide-ergic mechanisms can mediate the effects of inhaled β₂-adrenergic agonists. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 176–179, August, 2000     

Changes in mitotic activity in the corneal epithelium of rats of different ages after nociceptive stimulation

The effect of nociceptive stimulation on mitotic activity in the corneal epithelium was investigated in 21-day-old rat fetuses and in rats aged 3, 4, 5, 7, 10, 15, 20, and 25 days. Mitotic activity was not significantly changed 45 min after nociceptive stimulation of the animals (amputation of one-third of the tail) in the corneal of the fetuses and day-old rats. Between the 3rd and 10th days of postnatal development reactive inhibition of mitosis in response to nociceptive stimulation was gradually formed. After 10 days this response was intensified and reached a maximum by the 25th day. Reactive inhibition of mitotic activity is connected with delayed entry of the cells into mitosis.Department of General Biology, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol 82, No. 11, pp. 1367–1369, November, 1976.     

Hemodynamic effects of tetrindol in alert normotensive mice and rats after blockade of nitric oxide synthesis

Single intravenous injection of antidepressant tetrindol (1 and 10 mg/kg), a reversible monoamine oxidase A inhibitor, dose-dependently decreased heart rate and mean arterial pressure (in a concentration of 10 mg/kg) in alert NMRI mice and Sprague-Dawley rats. Nitric oxide synthase blockade with L-NAME attenuated tetrindol-induced bradycardia in rats and completely abolished this effect in mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 193–195, August, 2000     

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as novel a non-invasive marker of airway inflammation. OBJECTIVE: The level of exhaled NO was determined in a random sample of school children (7-12 years old) with the aim of investigating the relationship between exhaled NO and sensitization to common allergens. RESULTS: In the 450 children tested by skin prick tests (SPT), the prevalence of sensitization was 29.5% (overall), 21.9% (sensitization to indoor allergens), and 15.0% (sensitization to outdoor allergens). Regression analysis showed that levels of exhaled nitric oxide were closely associated with various measures of sensitization to aeroallergens. Sensitization to indoor allergens was associated with higher levels of exhaled NO (eNO) than sensitization to outdoor allergens when assessed by IgE but not when assessed by SPT. Children with reported wheeze in the past 12 months had much stronger associations between sensitization and eNO than children without wheeze. CONCLUSION: We conclude that allergic sensitization is strongly associated with increased levels of exhaled NO, especially in children with wheeze.     

Variation in plasma morphine level and pain sensitivity in prenatally morphinized rats

It is established that mature random-bred and Wistar rats exhibit the same level of pain sensitivity in the tail-flick test, but the analgetic effect of morphine (5 mg/kg) is variously expressed: marked hypalgesia is observed in mongrel but not in Wistar rats. Prenatal morphinization enhances the analgetic effect of morphine in both mongrel and Wistar rats. There is a direct correlation between the plasma morphine content in prenatally morphinized rats and their sensitivity to the analgetic action of morphine. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 273–275, September, 1995 Presented by D. A. Kharkevich, Member of the Russian Academy of Medical Sciences     

Intrathecal clonidine decreases spinal nitric oxide release in a rat model of complete Freund's adjuvant induced inflammatory pain

A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT) clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and antihyperalgesic effects of IT clonidine were examined post-treatment in a rat model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia. Using a chronic model of spinal cord dialysis, we examined the effect of the adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the development of chronic pain and assessed the antinociceptive effects and mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups receiving IT clonidine in discrete doses of 1, 10 or 50 g, 3 or 24 hr post-inflammation. Measurement of total NO _x (NO + ) was used to determine NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed using a radiant heat thermal hyperalgesia model. CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation. A dose-dependent suppression of thermal hyperalgesia and spinal NO release was observed after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain model suggests that clonidine's spinal antihyperalgesic mechanisms act through inhibition of spinal NO release.     

一氧化氮途径对大鼠精子发生的影响

为阐明一氧化氮途径对精子发生的影响 ,探讨一氧化氮对精子发生的调节作用 ,将雄性SD大鼠分为 4组 ,分别于腹腔内注射左旋精氨酸 (L arginine ,L ARG)、N 硝基左旋精氨酸甲酯 (N nitro L arginine mythel ester,L NAME)、L ARG +L NAME与生理盐水 ,每天一次 ,共 1 2d。于最后一次注射后 2h采血并处死动物。放免法测定血清内睾酮含量 ;GREISS法测定血清NO-x (硝酸盐 亚硝酸盐 )含量 ;常规组织学切片观察生精上皮形态 ,并对Ⅶ -Ⅷ期生精上皮横断面的各级生精细胞进行定量分析 ;扫描电镜观察生精小管内精子密度。结果表明 :L ARG组血清内NO-x 含量高于对照组 (P <0 0 1 ) ,睾酮含量低于对照组 (P <0 0 1 ) ,精子生成减少 (P <0 0 1 ) ;L NAME组血清内NO-x 含量低于对照组 (P <0 0 1 ) ,睾酮含量高于对照组 (P <0 0 1 ) ,精子生成增加 (P <0 0 1 )。L ARG +L NAME组NO-x 与睾酮含量及精子的生成无显著性变化。因此 ,加强NO途径抑制精子发生 ,抑制NO途径促进精子形成     

Hypotensive effect and tissue distribution of the dinitrosyl iron complexes, a nitric oxide donor

Hypotensive effect of the dinitrosyl iron complexes, an NO donor, is compared with distribution of these complexes in organs and tissues after their intravenous administration to wakeful animals. Hypotensive effect of iron complexes depended on dose and postinjection time. There was a strong correlation between hypotensive effect and the content of dinitrosyl iron complex in the studied organs. Effective dose of dinitrosyl iron complexes that did not provoke adverse effects was about 200 mg/kg. This preparation is a prospective source of NO to treat and prevent pathological states related to NO deficiency. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 1, pp. 30–33, January, 1998     

Increased generation of nitric oxide in tissues of rats following their adaptation to short-term stress (An EPR study)

Adaptation of rats to short-term immobilization stress increases the ability of their isolated organs to generate nitric oxide (NO): its spontaneous release by the liver, gut, heart, and kidney tissues rises 2- to 4-fold and its carbachol-stimulated release by these tissues rises 4- to 5-fold. It is suggested that such adaptation leads to rapid NO generation in the adapted animal in response to exogenous or endogenous stimuli and thus increases the efficacy of defense reactions. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 242–244, March, 1994 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

L-精氨酸和一氧化氮抑制剂对大鼠血管钙化的影响

观察给予一氧化氮合酶(NOS)的抑制剂左旋硝基精氨酸(L-NNA)或底物L-精氨酸(L-Arg)对血管钙化的影响。利用维生素D3和尼古丁制备大鼠血管钙化模型，测定大鼠尾动脉压，血管钙含量、碱性磷酸酶活性及^45Ca沉积；并检测血管组织的L-Arg转运，NOS活性及NO2^-和cGMP含量。发现钙化大鼠血压略升高；动脉钙含量、ALP活性及^45Ca沉积明显增加，von Kossa染色可以看到明显的钙化颗粒；钙化血管组织NOS活性升高；NO和cGMP含量均减少。给予L-NNA或L-Arg后，与单纯钙化组相比，L-NNA干预组的L-Arg转运、NOS活性及NO和cGMP的含量均降低；而L-Arg干预组上述指标的变化正相反。同时，L-NNA干预组的钙化程度比钙化组加重，而L-Arg干预组的钙化程度比钙化组减轻；提示血管钙化时NO—NOS—cGMP途径发生紊乱，干预NO—NOS—cGMP途径可以影响钙化的进程。     

The expression and activity of renal nitric oxide synthase and circulating nitric oxide in polycystic kidney disease rats

Nitric oxide (NO) influences tubular fluid and electrolyte transport, and hence possibly also fluid accumulation in renal cysts. The expression and activity of intrarenal constitutive NO synthase (cNOS) [neuronal NOS, nNOS and endothelial NOS, eNOS] and inducible NOS (iNOS) and plasma nitrite/nitrate (PNOx) concentration were assessed in homozygous Han:SPRD polycystic kidney disease (PKD) rats (cy/cy), heterozygous Han:SPRD PKD rats (cy/+), homozygous normal Han:SPRD littermates (+/+) and Sprague Dawley rats (sd). The results showed: 1) nNOS expression was decreased in proximal tubules and thick ascending limbs of the loop of Henle in cy/cy and cy/+ rats compared to +/+ and sd rats (p<0.05). nNOS was weakly expressed in the epithelium of small cysts and unexpressed in epithelium of large cysts. 2) iNOS expression was increased in proximal tubular epithelial cells in cy/+ rats compared to +/+ rats and sd rats (p<0.01). iNOS expression in cyst epithelium was decreased in cy/+ rats (p<0.05) and absent in cy/cy rats. 3) eNOS expression was similar in the endothelium of intrarenal arteries in all groups. 4) The activity of renal cNOS was decreased in cy/cy and cy/+ rats; the activity of iNOS was decreased only in cy/cy rats, with no significant difference among the other three groups. 5) PNOx concentration was higher in cy/cy rats than in the other three groups, and correlated positively with plasma creatinine and urea. In conclusion, NOS expression and activity decreased as cysts developed, suggesting that NO downregulation is involved in the pathogenesis of PKD.