Role of NO in vagally-mediated relaxations of guinea-pig stomach

Summary Vagal stimulation of the stomach induces a relaxation mediated via non-adrenergic, non-cholinergic (NANC) nerves. The neurotransmitter which is responsible for this relaxation is still unknown. To determine whether nitric oxide (NO) or a NO related substance mediates this relaxation, an intact guinea-pig stomach was mounted in an organ bath, with electrodes surrounding the vagal nerves.Electrical stimulation of the vagal nerves, in the presence of atropine, induced frequency dependent, tetrodotoxin-(TTX) sensitive relaxations of the stomach quantified as changes in volume. These relaxations were not affected by - or -adrenoceptor antagonists or guanethidine. Thus they were evoked by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. The relaxant responses could be inhibited in a concentration-dependent manner by N^G-nitro-Irarginine (IrNNA) a substance that inhibits the formation of nitric oxide (NO). Addition of L-arginine, the substrate for NO-synthase, reversed the L-NNA-induced-inhibition of the relaxation.Addition of nitroglycerin (a NO-donor) to a nonstimulated stomach mimicked the relaxations observed after vagal stimulation in a concentration dependent manner. These relaxations were insensitive to TTX. Relaxation of the stomach by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions.These data indicate that NO or a substance releasing NO plays an important role in NANC-neurotransmission after vagal stimulation of the guinea-pig stomach.Correspondence to A. L. Meulemans at the above address     

The role of nitric oxide (NO) in 5-HT-induced relaxations of the guinea-pig stomach

Summary In a previous study we showed that the relaxations induced after vagal stimulation of the guinea-pig stomach are mediated via nitric oxide (NO) or a NO-related substance. Intra-arterial injection (i.a.) of 5-hydroxytryptamine (5-HT) also induced relaxations in the guinea-pig stomach. Since it has been shown that in the guinea-pig colon 5-HT-induced relaxations are mediated via NO the aim of this study was to establish whether NO is involved in the 5-HT-induced relaxations in the guinea-pig stomach. Intra-arterial injection of 5-HT induced dose-dependent relaxations of the stomach. Since atropine and - and -adrenoceptor blocking agents did not influence the relaxation and since tetrodotoxin (TTX) blocked the relaxations, this effect is mediated via NANC-neurons. Administration of a NO-synthase-inhibitor N^G-nitro-l-arginine (L-NNA) concentration-dependently reduced the 5-HT-induced relaxations. Haemoglobin (a NO-scavanger) did not affect the relaxations to 5-HT, while addition of methylene blue, an inhibitor of soluble guanylate cyclase, reduced the relaxations by 50%. Addition of an opioid receptor agonist (loperamide), a 5-HT₁ antagonist (methiothepin or metergoline) or a 5-HT₄ receptor agonist (cisapride) or-antagonist (tropisetron in micromolar concentrations) inhibited the 5-HT-induced relaxations. Neither the 5-HT₄ receptor agonist renzapride, nor the novel 5-HT₄ receptor antagonist SDZ 205-557, affected the relaxations to 5-HT. These data indicate that 5-HT-induced relaxations of the guinea-pig stomach are mediated via NANC-inhibitory nerves on which inhibitory opioid-receptors are present. The use of selective agonists and antagonists indicates that 5-HT does not act via 5-HT₂, 5-HT₃ or 5-HT₄ receptors. 5-HT may act via 5-HT₁ receptors but the subtype involved, if any, has not yet been identified. The inhibitory neurotransmitter which is involved is NO or a NO-related substance. Correspondence to A. L. Meulemans at the above address     

Overnight storage of the porcine isolated splenic artery enhances endothelium-dependent contractions to NG-nitro-l-arginine methyl ester without impairing endothelium-dependent dilator function

This study examined the influence of overnight storage on endothelium-independent contractions to 5-hydroxytryptamine (5-HT), endothelium-dependent contractions to N^G-nitro-l-arginine methyl ester (L-NAME), and endothelium-dependent relaxations to substance P (SP) and l-arginine, using the porcine isolated splenic artery. In endothelium-intact (E+) segments from fresh porcine isolated splenic arteries or segments from the same vessels stored overnight at 4°C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline containing 1 MM l-arginine, 5-HT caused concentration-related contractions that were similar under all three conditions. Overnight storage enhanced contractions of the splenic artery to L-NAME, an effect not observed if the vessels were co0-stored with 1 MM l-arginine. L-NAME failed to contract endothelium-denuded (E–) segments from fresh tissues or tissues stored overnight, indicating that its constrictor effects were endothelium-dependent. SP caused concentration-related, endothelium-dependent relaxations of the splenic artery that were inhibited by 100 gM L-NAME, indicating that the relaxations could be attributed to the stimulated release of NO from endothelial cells. Established contractions to 100 M L,NAME in E+ segments from fresh tissues, or segments from the same tissues stored overnight at 4°C, either in KrebsHenseleit saline or in Krebs-Henseleit saline containing 1 MM l-arginine, were all reversed by 1 MM l-arginine to similar extents, indicating that overnight storage did not affect endothelium-dependent dilator responses to l-arginine. Our findings indicate that overnight storage enhances endothelium-dependent contractions to L-NAME without affecting endothelium-independent contractions to 5-HT, or endothelium-dependent dilator responses to SP or l-arginine. Correspondence to: V.G. Wilson at the above address     

Bronchorelaxation of the human bronchi by CFTR activators

The airway functions are profoundly affected in many diseases including asthma, COPD and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR (Cystic Fibrosis transmembrane Conductance Regulator) gene, which normally encodes a multifunctional and integral membrane cAMP regulated and ATP gated Cl⁻ channel expressed in airway epithelial cells.Using human lung tissues obtained from patients undergoing surgery for lung cancer, we demonstrated that CFTR participates in bronchorelaxation. Using human bronchial smooth muscle cells (HBSMC), we applied iodide influx assay to analyze the CFTR-dependent ionic transport and immunofluorescence technique to localize CFTR proteins. Moreover, the relaxation was studied in isolated human bronchial segments after pre-contraction with carbachol to determine the implication of CFTR in bronchodilation.We found in HBSMC that the pharmacology and regulation of CFTR is similar to that of its epithelial counterpart both for activation (using forskolin/genistein or a benzo[c]quinolizinium derivative) and for inhibition (CFTR_inh-172 and GPinh5a). With human bronchial rings, we observed that whatever the compound used including salbutamol, the activation of muscular CFTR leads to a bronchodilation after constriction with carbachol.Altogether, these observations revealed that CFTR in the human airways is expressed in bronchial smooth muscle cells and can be pharmacologically manipulated leading to the hypothesis that this ionic channel could contribute to bronchodilation in human.     

Regular aerobic exercise increases dispositional mindfulness in men: A randomized controlled trial

Dispositional mindfulness is a construct described as the propensity to be aware of one's actions in everyday life. Although high dispositional mindfulness has been demonstrated to be beneficial for improved mental and physical health, little is known about ways to improve dispositional mindfulness for individuals not practicing meditation or mindful exercises. The study aimed at investigating (1) whether dispositional mindfulness can also be trained by regular aerobic exercise and (2) whether changes in dispositional mindfulness are associated with changes in mental and physical health. 149 healthy men were randomly allocated to one of two 12-week interventions (aerobic exercise or relaxation training) or a waitlist control condition. Dispositional mindfulness and mental and physical health were assessed before and after the intervention by self-report questionnaires. Over the course of the intervention, increases in dispositional mindfulness occurred in the aerobic exercise group but not in the relaxation or waitlist control conditions (p = .018). Increases in dispositional mindfulness were moderately correlated with improvements in mental health. For the first time, this study shows that dispositional mindfulness can be increased through regular aerobic exercise. Future research is needed to identify how the mindfulness-enhancing potential of aerobic exercise can be used most effectively.     

Frequency-dependent acceleration of relaxation in the heart depends on CaMKII,but not phospholamban

Frequency-dependent acceleration of relaxation (FDAR) is an intrinsic physiological mechanism, which allows more rapid ventricular diastolic filling at higher heart rates. FDAR is also observed in isolated myocardial trabeculae and cardiac myocytes, but its mechanism is still poorly understood. We tested the hypothesis that FDAR results mainly from Ca/calmodulin-dependent protein kinase II (CaMKII) dependent stimulation of sarcoplasmic reticulum (SR) Ca transport, but does not require phospholamban. Experiments were performed at 23 or 35 degrees C in isolated ventricular muscle and single myocytes from wild-type (WT) and phospholamban knockout (PLB-KO) mice and rat ventricular myocytes. Isometric twitch force of muscles and unloaded shortening and Ca transients in myocytes were measured ([Ca](o)=1mM) in the absence and presence of CaMKII inhibitors (1 microM KN-93 or 20 microM autocamtide-2 related inhibitory peptide, AIP). Stimulation frequency was altered over a wide range (0.2-8Hz) and post-rest vs steady state twitches were also compared. In both WT and PLB-KO mouse muscles FDAR of twitch force was prominent, but was largely suppressed by KN-93. FDAR of twitch contractions was associated with FDAR of Ca transients in PLB-KO myocytes, and both were inhibited by KN-93. Similarly, a different CaMKII inhibitor (AIP) inhibited FDAR of contraction and Ca transients in rat ventricular myocytes. We conclude that FDAR results mainly from CaMKII-dependent stimulation of SR Ca transport, but does not require phospholamban.     

心理干预联合放松训练对晚期癌痛患者疼痛程度及睡眠的影响探讨

目的：观察对晚期癌痛患者施以心理疏导和放松训练联合干预方式的临床应用效果。方法选择2013年12月—2014年12月在该院住院治疗的晚期癌痛病例1000例做为研究对象,随机分为试验组500例与对照组500例,对照组施以一般护理内容,试验组则于对照组护理内容基础之上加用心理干预联合放松训练干预,比较两组晚期癌痛病例干预后相关指标的差异性。结果试验组晚期癌痛病例干预后疼痛评分、PSQI评分均显著低于对照组入选对象(P<0.05)。结论对晚期癌痛患者施以心理疏导和放松训练联合干预,能够显著降低该类患者的癌痛程度,改善其睡眠质量,具有现实的推广价值。     

Development of Tolerance to Inhibitory Effect of Ethanol on Endothelium-dependent Vascular Relaxation in Ethanol-fed Rats

Rats were maintained on liquid diets containing ethanol (35% of total calories) or an equicaloric volume of sucrose instead of ethanol for 10 wk. Vascular strips of isolated rat aortas were mounted in organ chambers to record isometric tension. Ethanol in vitro inhibited the endothelium-dependent relaxation responses to acetylcholine and ATP in both pair-fed control and ethanol-fed rats. The inhibitory effect of ethanol was greater in the pair-fed rats. In addition, the magnitudes of these relaxation responses in the absence of ethanol in vitro in pair-fed rats were similar to those in the presence of ethanol in ethanol-fed rats. In the absence of ethanol in vitro, the relaxations in response to acetylcholine and ATP in the ethanol-fed rats were greater than in the pair-fed rats. These results suggest that chronic ethanol consumption can induce tolerance to ethanol-induced inhibition of endothelium-dependent relaxation responses to acetylcholine and ATP, and that the relaxations can become adapted to the presence of plasma levels of ethanol, which may inhibit the relaxation in vivo. The augmented relaxation in the ethanol-fed rats may result from the mechanism causing tolerance to the inhibitory effect of ethanol.     

The effect of jaw relaxation on pain anxiety during burn dressings: Randomised clinical trial

Aim

The purpose of this randomised clinical trial (RCT) was to determine the effect of jaw relaxation on pain anxiety related to dressing changes in burn injuries.

Introduction

Patients hospitalised with burns experience high levels of anticipatory anxiety during dressing changes, which cannot be completely managed by anxiolytic drugs. Nurses as members of the burn care team contribute to pain management by using relaxation techniques as one of the most frequently used approaches to pain anxiety management. However, there is not enough information about the effects of these techniques on pain anxiety of patients with burns. The aim of this study was to determine the effect of jaw relaxation on pain anxiety related to dressing changes in burn injuries.

Methods

It was a randomised clinical trial with a control group. A total of 100 patients hospitalised in Shahid Motahari Burn Centre affiliated with Tehran University of Medical Sciences were recruited by convenience sampling and were randomly assigned to either experimental or control groups using minimisation. With institutional approval and written consent, the experimental group practiced jaw relaxation for 20 min before entering the dressing room. Data were collected by the Burn Specific Pain Anxiety Scale (BSPAS) during July–December 2009 and analysed using Statistical Package for the Social Sciences (SPSS)-PC (17).

Results

An independent t-test showed no significant difference between mean pain anxiety scores in the experimental and control group before intervention (p = 0.787). A dependent t-test showed significantly less pain anxiety after intervention (before dressing) in the experimental group (p < 0.05). Moreover, the independent t-test showed that the post-dressing pain anxiety of the experimental group was less than the control group (p < 0.05). However, the dependent t-test showed no significant difference between before and after dressing pain anxiety (after intervention) in the experimental group (p = 0.303).

Conclusion

Nurses can independently decrease the pain anxiety of patients with burns and its subsequent physical and psychological burden by teaching the simple and inexpensive technique of jaw relaxation. Further research is needed to study the effect of this technique on pain anxiety of patients suffering from other painful procedures.