The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries

In a previous survey concerning cows of reproductive age, we demonstrated that oocytes isolated from ovaries with <10 medium antral follicles of 2 to 6 mm in diameter (low ovaries; Lo) show less developmental competence than oocytes collected from ovaries with >10 medium antral follicles (high ovaries; Hi). The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce oocyte competence from Lo ovaries. Thus, experiments were conducted to 1) immunolocalize eNOS protein during folliculogenesis; 2) quantify eNOS protein/vasculature in the follicle wall; and 3) verify if NO donor, S-nitroso acetyl penicillamine (SNAP) administration during in vitro maturation affects developmental competence of oocytes isolated from Lo ovaries. Endothelial nitric oxide synthase protein was detected in granulosa and theca cells, as well as in blood vessels from primordial to antral follicles. Quantitative analysis indicated that in medium antral follicles from Lo ovaries, eNOS protein expression and vasculature were reduced (P < 0.05). The addition of SNAP improved blastocyst and hatching rates of oocytes from Lo ovaries, promoting a percentage similar to oocytes from Hi ovaries, and reduced the percentage of apoptotic nuclei in in vitro-produced blastocysts (P < 0.05). Results from our study suggest that in bovine ovaries with small mid antral follicle number, a defective eNOS/NO system is related to a reduced follicle vasculature and may affect oocyte quality, thus inducing a premature decline of fertility.     

Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens

Pulmonary arterial remodelling is a pathological characteristic of pulmonary arterial hypertension (PAH), which contributes to the development of sustained pulmonary hypertension. The aim of this study was to investigate the effects of dietary Trifolium pratense isoflavones on pulmonary vascular remodelling in experimental broiler pulmonary hypertension syndrome. Exposure to sub‐thermoneutral environmental temperatures increased broiler's pulmonary hypertension syndrome incidence and raised expression levels of nitric oxide, endothelin and endothelial nitric oxide synthase. Dietary supplementation (20 mg/kg basal diet) with Trifolium pratense isoflavones reduced pulmonary hypertension syndrome incidence and improved pulmonary vascular remodelling without affecting growth performance. The beneficial effect likely came from isoflavone improved pulmonary vascular remodelling. Isoflavone induced inducible nitric oxide synthase expression, which led to increased nitric oxide level. The nitric oxide could mediate vasorelaxation in the lungs. At the same time, the expression of endothelin was downregulated by isoflavone. Dietary supplementation of Trifolium pratense isoflavone might be a potential therapeutic strategy for the treatment of pulmonary hypertension.     

Toll-like receptor mRNA expression, <Emphasis Type="Italic">iNOS</Emphasis> gene polymorphism and serum nitric oxide levels in indigenous chickens

Toll-like receptor (TLR) family is one of the important members of innate immune system that recognizes conserved microbial patterns and induces innate immune response. They also act as a link to adaptive immune response. Nitric oxide (NO) is a multi-functional mediator with diverse physiological and immunological roles. In the present study TLR mRNA expression in heterophils, serum nitric oxide level and iNOS (inducible Nitric Oxide Synthase) gene polymorphism were investigated in cockerels of two Indian native chicken breeds, Aseel and Kadaknath. TLR (4 and 5) mRNA expression as quantified by real time RT-PCR revealed Kadaknath males expressed significantly (P < 0.01) higher TLR4 mRNA than Aseel males. iNOS gene polymorphism analyzed by PCR-RFLP method revealed difference in allele frequency. Kadaknath males had higher allele B frequency (0.81) than Aseel males (0.56). However, there were no genotype and breed effect on serum nitric oxide level. Based on the present study we conclude that Kadaknath has comparatively higher innate immunity levels than Aseel, however further investigations are needed.     

Parthenogenetic Activation of Pig Oocytes Using Pulsatile Treatment with a Nitric Oxide Donor

The nitric oxide donor (+)–S‐nitroso‐N‐acetylpenicillamine (SNAP) is capable of inducing parthenogenetic activation in pig oocytes matured in vitro. However, quite a long exposure to the nitric oxide donor, exceeding 10 h, is necessary for successful oocyte activation. Repeated short‐term treatment with 2 mm SNAP significantly increased the activation rates despite the fact that the overall exposure time to the nitric oxide donor did not exceed 4 h. With regard to the activation rate, 12 repeated treatments lasting 10 min each were found to be the most efficient regimen (63.3%). The continuous exposure to the nitric oxide donor for the same overall time induced parthenogenetic activation in 12.5% oocytes (2‐h continuous treatment with 2 mm SNAP). The development of parthenogenetic embryos increased after repeated short‐term treatment with SNAP. After continuous treatment with 2 mm SNAP for 10 h, only 6.7% of the oocytes cleaved, and none developed beyond the 4‐cell stage. Thirty‐minute treatment repeated four times with 2 mm SNAP induced cleavage in 37.5% of the oocytes, 18.3% developed to the morula stage, and 6.7% reached the blastocyst stage. Based on the results, it is concluded that pulsatile treatment can significantly improve parthenogenetic activation rate when compared with the continuous treatment using nitric oxide donors.     

The effects of hyperoxia on the biosynthesis of cyclooxygenase products and haemodynamic response to nitric oxide synthase inhibition with L-NAME in endotoxaemic pigs

The interaction between constitutive nitric oxide and oxygen may depend on the degree of tissue oxygenation and may play a critical role in the pathophysiological response to endotoxaemia. We investigated if hyperoxia (100% O₂) attenuated the systemic and pulmonary vasoconstriction and increased biosynthesis of thromboxane B₂ (TXB₂) and 6-keto-prostaglandin (PG) F_1α induced by inhibition of nitric oxide synthase with N^G-nitro-l -arginine-methyl-ester (L-NAME) in a porcine model of endotoxaemia. Twenty-two domestic, random source pigs, weighing 15.4 ± 2.7 kg (mean ± standard deviation) were the subjects of this study. Pigs were anaesthetized with isoflurane in 100% O₂, orotracheally intubated and ventilated to maintain normocapnia, and then instrumented for haemodynamic monitoring. Following instrumentation, pigs were maintained at an end-tidal isoflurane concentration of 2%. Pigs were randomly assigned to treatment groups: saline + 30% O₂ (Control, n = 6); Escherichia coli lipopolysaccharide (5 μg/kg/h from 1 to 2 h followed by 2 μg/kg/h from 2 to 5 h) + 30% O₂ (LPS, n = 4); L-NAME (0.5 mg/kg/h, from 0 to 5 h) + LPS + 100% O₂ (n = 6); and L-NAME + LPS + 30% O₂ (n = 6). L-NAME and endotoxin significantly (P < 0.05) increased mean arterial pressure, mean pulmonary arterial pressure, and systemic and pulmonary vascular resistance index beginning at 90 min. When results were pooled across all time periods, mean arterial pressure and mean pulmonary arterial pressure were significantly higher in the L-NAME + LPS + 30% O₂ group than all other groups, reflecting pulmonary and systemic vasoconstriction. Hyperoxia attenuated the L-NAME + LPS-induced increases in TXB₂ and 6-keto-PGF_1α concentrations at 90 and 120 min and 120 min, respectively, although the differences were not statistically significant. These results support the observation that nitric oxide synthase inhibition with L-NAME has deleterious haemodynamic effects in this model of endotoxaemia. The temporal attenuation of L-NAME-induced pulmonary and systemic vasoconstriction by hyperoxia suggested that the haemodynamic effects of acute endotoxaemia were in part influenced by the relative amounts of nitric oxide and oxygen present.     

吸胀冷害下外源NO对紫花苜蓿种子萌发及抗氧化性的影响

用浓度为0.1 mmol/L外源NO供体硝普钠(sodium nitroprusside,SNP)处理4℃吸胀冷害下紫花苜蓿种子,来探讨吸胀冷害下NO对紫花苜蓿种子萌发及氧化损伤的影响。试验设计4个处理,分别为A:对照组(CK)为蒸馏水;B:4℃吸胀冷害组(Chilling);C: SNP;D:Chilling+SNP,每个处理重复3次。结果表明:1)紫花苜蓿种子经SNP处理12 h转入25℃继续培养84 h后,Chilling+SNP组比Chilling组发芽率、活力指数、发芽指数提高了14.37%,34.17%,1.29%。2)4℃吸胀冷害12 h后,Chilling+SNP组同Chilling组相比超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性分别提高了149.26%,60.35%,过氧化氢(H₂O₂)含量及超氧阴离子(·O₂^-)产生速率则降低了10.11%,27.61%。3)SNP对4℃吸胀冷害12,24和48 h 的种子体内羟自由基(·OH)的清除均呈下降趋势,Chilling+SNP组的清除率均高出SNP组,Chilling+SNP组在冷害12 h时清除率达最大值97.5%。综上所述,施加外源NO能促进种子的萌发,提高抗氧化酶活性,降低了活性氧对种子造成的伤害。     

Follicular characteristics and intrafollicular concentrations of nitric oxide and ascorbic acid during ovarian acyclicity in water buffalo (Bubalus bubalis)

The objective of this study was to examine the follicular characteristics and intrafollicular concentrations of nitric oxide and ascorbic acid during ovarian acyclicity in buffaloes. Ovaries were collected from 56 acyclic and 95 cyclic buffaloes at slaughter, surface follicle number was counted and follicles were classified into small (5.0–6.9 mm), medium (7.0–9.9 mm), and large (≥10.0 mm) size categories based on their diameter. Follicular fluid was aspirated and assayed for nitric oxide, ascorbic acid, estradiol, and progesterone. Acyclic buffaloes had a higher (P < 0.05) number of medium-sized follicles and a lower (P < 0.001) number of large follicles than the cyclic ones. In acyclic animals, the number of large follicles was lower (P < 0.01) than in medium size category which in turn was lower (P < 0.001) than the number of small follicles. In contrast, the number of medium and large follicles was not different (P > 0.05) in the cyclic control. However, the number of small-sized follicles was higher (P < 0.001) compared to the other two categories. The incidence of large-sized follicles was lower (P < 0.05) in acyclic buffalo population compared to the cyclic control. Evaluation of estrogenic status demonstrated that all the follicles of acyclic buffaloes are estrogen-inactive (E ₂/P ₄ ratio < 1). Small- and medium-sized follicles of acyclic buffaloes had higher concentrations of nitric oxide (P < 0.05 and P < 0.001, respectively) and lower concentrations of ascorbic acid (P < 0.05 and P < 0.01, respectively) than the corresponding size estrogen-active follicles of their cyclic counterparts. In conclusion, this study indicates that follicular development continues during acyclicity in buffaloes. Although follicles in some acyclic buffaloes attain a size corresponding to morphological dominance, they are unable to achieve functional dominance, perhaps due to an altered balance of intrafollicular nitric oxide and ascorbic acid and, as a result, these follicles instead of progressing to ovulation undergo atresia.     

Relationships among vasculature,mitotic activity,and endothelial nitric oxide synthase (eNOS) in bovine antral follicles of the first follicular wave

To determine the relationships among vasculature, mitotic activity, and expression of endothelial nitric oxide synthase (eNOS) of antral follicles in Bos indicus, bovine ovaries were obtained on day 6 of the estrous cycle from 10 crossbred (Brahman to Thai native cows) after a synchronized estrus with prostaglandin F₂α analogue. Ovaries were fixed, paraffin-embedded, and used for immunofluorescence detection of factor VIII (a marker of endothelial cells). Immunostaining of eNOS and proliferating cell nuclear antigen (PCNA) were performed with specific monoclonal antibodies. Vasculature and positive staining of eNOS and PCNA were quantitatively evaluated with the image analysis. Follicles were classified by size (small, medium, and large) and by structure as healthy and atretic follicles (n = 82). The expression of factor VIII and eNOS were detected greater in the blood vessels of the theca layers of the healthy follicles than those in atretic follicles. The labeling indices (LIs) in granulosa and theca cells were greater (P < 0.05) in the healthy small and medium follicles than in the healthy large follicles. Vasculature, capillary area density, and capillary number density were positively correlated with eNOS expression and the LIs of granulosa and theca cells but were negatively correlated with the healthy follicle size. During the growing phase of antral follicle in Bos indicus, relationships among vasculature, mitotic activity, and eNOS were observed predominantly in healthy antral follicles. Thus, these data highlight the importance of vasculature, cell proliferation, and eNOS expression of growing and atretic follicles in the first follicular wave.     

Selenium stimulates estradiol production in bovine granulosa cells: possible involvement of nitric oxide

Reduction in fertility is well known to be possibly related to selenium deficiencies, even if target organ for selenium action is, at present, unclear. The present study was aimed to examine whether selenium directly influences granulosa cells. Bovine granulosa cells from different size follicles were used to investigate the effect of selenium (5 ng/ml), with or without bovine follicle-stimulating hormone (bFSH) (100 ng/ml), on proliferation and steroidogenesis. In addition, we sought to determine if selenium modulates the production of nitric oxide, which is known to play an important role in ovarian activity. Our data demonstrate that selenium significantly (P < 0.001) stimulates the proliferation of the cells from small follicles; moreover, it further potentiates the stimulatory effect of the gonadotropin in the same cells. Furthermore, selenium significantly (P < 0.01) augments E2 output by cells from both kinds of follicles. bFSH increases E2 production (P < 0.01) by cells from large follicles, whereas it exerts a stimulatory (P < 0.01) effect only in the presence of selenium in the cells from the small ones. The production of nitric oxide is significantly increased (P < 0.001) by bFSH, but only in cells from small follicles. Selenium inhibits (P < 0.001) nitric oxide production in cells from both kinds of follicles and significantly decreases (P < 0.001) bFSH-induced nitric oxide production in cells from the small ones. We conclude that selenium acts on granulosa cells by modulating their proliferation and E2 synthesis; moreover, its effect could be mediated, at least in part, through an inhibition of nitric oxide.     

Nitric oxide,inducible nitric oxide synthase and inflammation in veterinary medicine

Inflammation is a process consisting of a complex of cytological and chemical reactions which occur in and around affected blood vessels and adjacent tissues in response to an injury caused by a physical, chemical or biological insult. Much work has been performed in the past several years investigating inducible nitric oxide synthase (NOS, EC 1.14.13.39) and nitric oxide in inflammation. This has resulted in a rapid increase in knowledge about iNOS and nitric oxide. Nitric oxide formation from inducible NOS is regulated by numerous inflammatory mediators, often with contradictory effects, depending upon the type and duration of the inflammatory insult. Equine medicine appears to have benefited the most from the increased interest in this small, inflammatory mediator. Most of the information on nitric oxide in traditional veterinary species has been produced using models or naturally occurring inflammatory diseases of this species.     

Does the renal portal valve exist in a raptor species? A study aimed at further evaluating the mechanism of toxicity of diclofenac in vultures

Diclofenac has been responsible for the deaths of millions of vultures on the Asian subcontinent. While the pathology of toxicity is well described, the mechanism of toxicity remains elusive. However, it was postulated that toxicity could be related to the unique avian renal vascular structure known as the renal portal valve and that that diclofenac altered valve functionality with subsequent renal ischaemia. While plausible, the valva renalis portalis has only been described in a small number of other bird species such as the chicken (Gallus domesticus), the domestic duck (Anas platyrhynchos domesticus) and ostrich (Struthio camelus) but not a raptor. The aim of this study was to evaluate the renal anatomy and related vasculature of the Cape griffon vulture (Gyps coprotheres) (CGV), a species sensitive to the toxic effects of diclofenac, using gross anatomy, histology and vascular casting. The vasculature of the vulture was found to be almost identical to that of the domestic chicken with the valva renalis portalis present in the v. iliaca externa between the v. renalis renalis cranialis and the v. renalis caudalus. The valve was ring-shaped with finger-like processes and histologically was composed of smooth muscle. The valve was also well vascularized and was associated with a nerve plexus. Based on the findings of this study, the proposed mechanism of toxicity is anatomically possible.     

The inhibitory effect of quercitrin gallate on iNOS expression induced by lipopolysaccharide in Balb/c mice

Quercetin 3-O-β-(2"-galloyl)-rhamnopyranoside (QGR) is a naturally occurring quercitrin gallate, which is a polyphenolic compound that was originally isolated from Persicaria lapathifolia (Polygonaceae). QGR has been shown to have an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Therefore, this study was conducted to investigate the inhibitory effect of QGR on nitric oxide production and inducible nitric oxide synthases (iNOS) expression in LPS-stimulated Balb/c mice. To accomplish this, 10 mg/kg of QGR was administered via gavage once a day for 3 days. iNOS was then induced by intraperitoneal injection of LPS. Six hours after the LPS treatment the animals were sacrificed under ether anethesia. The serum levels of NO were then measured to determine if QGR exerted an inhibitory effect on NO production in vivo. LPS induced an approximately 6 fold increase in the expression of NO. However, oral administration of QGR reduced the LPS induced increase in NO by half. Furthermore, RT-PCR and western blot analysis revealed that the increased levels of iNOS expression that occurred in response to treatment with LPS were significantly attenuated in response to QGR pretreatment. Histologically, LPS induced the infiltration of polymorphonuclear neutrophils in portal veins and sinusoids and caused the formation of a large number of necrotic cells; however, pretreatment with QGR attenuated these LPS induced effects. Taken together, these results indicate that QGR inhibits iNOS expression in vivo as well as in vitro and has antiinflammatory potentials.     

Effects of Bacillus subtilis B10 spores on viability and biological functions of murine macrophages

This study was conducted to investigate the effects of Bacillus subtilis B10 spores on the viability and biological functions of murine macrophage. RAW 264.7 cells were stimulated both with and without B. subtilis B10 spores for 12 h. Then cell viability was determined to evaluate the cytotoxic effect of B. subtilis B10 spores to the cells, and the activities of acid phosphatase (ACP) and lactate dehydrogenase (LDH), the production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), and the secretion of inflammatory cytokines were measured to analyze the functions of macrophages. The results showed that B. subtilis B10 spores were not harmful to RAW 264.7 cells and they also strongly enhanced the activities of ACP and LDH (P < 0.01), remarkably increased NO and iNOS production (P < 0.01), and significantly stimulated the secretion of pro‐inflammatory cytokines, including tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐1 beta (IL‐1β), IL‐6, IL‐8 and IL‐12 (P < 0.01) while they reduced anti‐inflammatory cytokine IL‐10 (P < 0.01). The outcomes suggest that B. subtilis B10 spores are not only safe for murine macrophages, but also can activate these cells and enhance their immune function. The above findings suggest that B. subtilis B10 spores are potentially probiotic.     

Effect of inhaled nitric oxide on the hypoxic pulmonary vasoconstrictor response in anaesthetised calves

The effect of inhaling nitric oxide in the hypoxic pulmonary vascular response was measured in five calves anaesthetised with a combination of guaiacol, ketamine and xylazine. Alveolar hypoxia was induced by means of the inhalation of a gas mixture with an inspiratory oxygen fraction of 14–18 per cent. This alveolar hypoxia resulted in a pronounced pulmonary hypertension (mean pulmonary artery pressure in hypoxic animals : 30·2 mmHg). Inhalation of 20 and 40 ppm of nitric oxide significantly attenuated the hypoxia induced pulmonary hypertension. The effect ceased once nitric oxide administration was stopped. A concentration of 40 ppm of nitric oxide fully abolished the hypoxia induced pulmonary hypertension (mean pulmonary artery pressure during inhalation of 40 ppm nitric oxide : 22·8 mmHg). Inhalation of nitric oxide had no effect on systemic arterial blood pressure nor on systemic vascular resistance. It was concluded that inhalation of 20 or 40 ppm of nitric oxide prevented a selective pulmonary vasoconstriction during alveolar hypoxia in calves, which may be helpful in the treatment of acute respiratory disorders in calves.     

NO参与Spd诱导白三叶抗氧化酶活性及其基因表达

以‘拉丁诺’白三叶为试材,采用药理学实验,探讨一氧化氮(NO)信号在外源亚精胺(Spd)诱导抗氧化酶活性及其基因表达中的作用。研究结果显示,20 μmol/L的外源Spd可显著提高白三叶叶片硝酸还原酶(NR)和一氧化氮合酶(NOS)活性,诱导白三叶离体叶片NO积累,并且具有时间效应,在处理第2 h达到最大值;50 μmol/L NO清除剂牛血红蛋白(Hb)、5 mmol/L 硝酸还原酶(NR)抑制剂偏钒酸钠(NaVO₃)以及200 μmol/L一氧化氮合酶(NOS)抑制剂NG-硝基-L-精氨酸甲酯盐酸盐(L-NAME)处理均可不同程度地逆转Spd诱导的NO含量的升高。外源Spd亦可提高白三叶叶片超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)和抗坏血酸过氧化物酶(APX)的活性及其基因的相对表达量,而Hb、NaVO₃和L-NAME不同程度地抑制了Spd诱导的SOD、POD、CAT、APX酶活性及其基因表达。以上结果表明:Spd可能通过激活硝酸还原酶和一氧化氮合酶途径诱导产生NO,且NO信号参与了Spd调控白三叶叶片抗氧化酶活性及其基因表达。     

Effect of l-arginine methyl ester (l-NAME) on hormonal profile and estrous cycle length in buffaloes (Bubalus bubalis)

The present study was undertaken to evaluate the effect of L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor on serum nitric oxide, progesterone, estradiol profiles and estrous cycle length in buffaloes. Murrah buffaloes (n?=?16) exhibiting regular estrous cycles were randomly allocated to two groups of eight animals. In the treatment group, buffaloes were administered 400?mg/h?L-NAME over 2?h (total dose?=?800?mg) via the coccygeal artery and the aorta abdominalis on day 15 of the estrous cycle. In the control group, normal saline was infused on the same day of the cycle by the same route. Blood samples were collected every 4?h on days 15 and 16, and once daily from days 17 to 21 of the estrous cycle for the assay of progesterone, estradiol and nitric oxide. L-NAME treatment significantly (p?相似文献   

Pulsed delivery of nitric oxide counteracts hypoxaemia in the anaesthetized horse

Objective To study the effect of the pulsed delivery of nitric oxide (NO) on pulmonary gas exchange in the anaesthetized horses. Design Prospective, controlled randomized. Animals Five healthy Standardbred trotters, three geldings and two mares. Methods The horses were anaesthetized with thiopentone and isoflurane and positioned in dorsal recumbency. Nitric oxide was added as a pulse to the inspired gas during the first half of each inspiration. In three horses the effect of NO on the ventilation–perfusion distribution was also investigated using the multiple inert gas elimination technique. Data were analysed with repeated measures ANOVA. Results During spontaneous breathing, arterial oxygen tension (PaO₂) increased with NO inhalation, from 14 ± 2 to 29 ± 3 kPa (105 ± 15 to 218 ± 23 mm Hg) (p < 0.001). Arterial oxygen tension also increased, from 17 ± 3 to 31 ± 5 kPa (128 ± 23 to 233 ± 38 mm Hg) (p < 0.05) during intermittent positive pressure ventilation. The increase in PaO₂ was mainly due to a reduced right to left vascular shunt, but ventilation and perfusion matching also improved. The beneficial effect of NO inhalation was lost within 5 minutes of its discontinuation. Conclusion Delivery of NO as a pulse during inspiration is an effective method for counteracting impaired gas exchange caused by anaesthesia in horses. Pulsation has to be continuous because of the transience of NO's therapeutic effect. Clinical relevance Horses with impaired pulmonary gas exchange during anaesthesia can be treated with pulsed NO inhalation.     

L-arginine prevents reduced expression of endothelial nitric oxide synthase (NOS) in pulmonary arterioles of broilers exposed to cool temperatures

This study investigated nitric oxide synthase (NOS) expression in the endothelium of pulmonary arterioles of broilers during the development of pulmonary hypertension syndrome (PHS). PHS was triggered by exposing broilers to sub-thermoneutral (cool) temperatures and an additional 1.0% L-arginine was added to the basal diet to evaluate the effects of supplemental L-arginine on nitric oxide (NO) production, endothelial NOS expression, and the incidence of PHS. Cumulative mortality from PHS, right/total ventricle weight ratios (RV/TV), and body weights were recorded. Plasma NO concentration and NOS expression in the endothelium of pulmonary arterioles with an outer diameter ranging from 100 to 200 microm were determined. Birds exposed to cool temperatures had increased pulmonary hypertension and PHS mortality and diminished endothelial NOS expression. Supplemental dietary L-arginine reduced PHS mortality and elicited higher NOS expression within the pulmonary endothelium coincident with elevated NO production. The results demonstrated that broilers developing PHS exhibited diminished NOS expression in the endothelium of their pulmonary arterioles. Supplemental L-arginine prevented the reduced expression of NOS in the pulmonary endothelium, which might contribute to the increased production of NO by the pulmonary vasculature.     

Pentoxifylline pretreatment fails to block the acute-phase response toEscherichia coli endotoxin in dwarf goats

The purpose of this study was to assess whether pentoxifylline, a drug that can inhibit the production and action of pro-inflammatory cytokines, had beneficial effects on the acute-phase response toE. coli endotoxin in the dwarf goat. First, the effects of 0.5 mg/kg per min pentoxifylline given intravenously over 15 min were examined in five goats. One week later, the clinical changes caused by i.v. injection ofE. coli endotoxin (LPS: 0.1 µg/kg) were determined. This endotoxin induced fever, tachycardia, inhibition of rumen motility, and decreases in plasma zinc and iron concentrations. Three weeks later, the effects ofE. coli LPS were again determined immediately after pentoxifylline infusion in the same group of animals. It was concluded that a pharmacological dose of pentoxifylline has no protective effects on the acute-phase response reactions induced by a pyrogenic dose ofE. coli LPS Abbreviations AMP adenosine phosphate - APR acute-phase response - GMP guanosine phosphate - IL interleukin - i.v. intravenous - LPS lipopolysaccharides - NO nitric oxide - POF pentoxifylline - r recombinant - SEM standard error of mean - TNF tumour necrosis factor