Effect of vasoactive intestinal polypeptide on the canine cardiovascular system

Our purpose was to determine the effect of vasoactive intestinal polypeptide (VIP) on the cardiovascular system with special emphasis on coronary vascular effects. In section I, VIP was infused into six healthy and six cobalt-cardiomyopathic dogs at two infusion rates (0.02 and 0.05 micrograms/kg/min). Left ventricular end diastolic pressure and mean systemic pressure fell significantly in both groups. Heart rate rose in both, and maximum systolic dP/dt increased in the myopathic group. Cardiac output and regional blood flows were determined by serial left atrial injections of radioactive 15 +/- 3 mum (mean +/- SD) microspheres. In both groups, blood flow increased significantly to the esophagus, pancreas, atria, and ventricles and to the endocardial and epicardial regions of the left ventricular free wall. Blood flow to the brain decreased. In section II, VIP was infused intravenously at 0.1 micrograms/kg/min into six anesthetized dogs with coronary sinus flow, pulmonary artery, and systemic artery catheters inserted. Cardiac index rose from baseline (3.1 +/- 0.5 to 4.8 +/- 1.3 L/min/m2, P less than 0.005), as did coronary blood flow (90 +/- 25 to 159 +/- 54 ml/min, P less than 0.005) during the VIP infusion. Myocardial oxygen consumption rose from 14.1 +/- 3.9 to 19.8 +/- 5.4 ml/min (P less than 0.001), but the aorta-to-coronary sinus O2 difference decreased from 157 +/- 19 ml/L to 132 +/- 42 ml/L (P less than 0.05), and the percent O2 extracted from coronary blood also decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

神经肽Y和血管活性肠肽对婴幼儿充血性心力衰竭调控作用的研究

目的：探讨血浆神经肽Ｙ（ＮＰＹ）和血管活性肠肽（ＶＩＰ）在婴幼儿充血性心力衰竭过程中的变化及其意义。方法：对３０例急性充血性心力衰竭婴幼儿和３０例正常婴幼儿的血浆ＮＰＹ和ＶＩＰ进行放射免疫测定,并对研究组中的１８例于治疗症状控制后用同样方法复查ＮＰＹ和ＶＩＰ含量。结果：研究组治疗前的血浆ＮＰＹ和ＶＩＰ水平分别为（２９９．７３±１３０．９９）ｎｇ／Ｌ和（３７．１５±１０．５２）ｎｇ／Ｌ,均明显高于正常对照组（７９．５３±２４．５１）ｎｇ／Ｌ和（１０．２８±７．６９）ｎｇ／Ｌ（Ｐ均＜０．０１）。ＮＰＹ升高的程度与心功能有关,心力衰竭越重,ＮＰＹ的含量越高。症状控制后血浆ＮＰＹ水平由（３０１．１１±１３１．７２）ｎｇ／Ｌ降至（１６２．８３±６７．２９）ｎｇ／Ｌ,而ＶＩＰ仍维持在较高水平〔（３９．０８±１０．３０）ｎｇ／Ｌ～（４１．１１±７．４１）ｎｇ／Ｌ〕。结论：ＮＰＹ对心力衰竭的发病有重要病理生理意义,血浆ＮＰＹ含量升高,可作为婴幼儿心力衰竭严重程度和预后不良的指标。维持ＶＩＰ的高水平,有助于对心力衰竭病理过程的控制,为治疗心力衰竭提供一新的途径     

快速心室起搏犬心房颤动模型研究

目的建立快速起搏心室致心力衰竭犬房颤模型,研究其电生理及心房结构和功能改变。方法 15只健康杂种犬分两组:对照组6只,实验组9只[240次/min心室起搏(25±3)d]。超声心动图测定起搏前后心房面积、面积缩小分数及左心室功能,利用心内电极测定心房有效不应期、传导速度及房颤诱发情况。结果实验组7只犬完成了实验。快速心室起搏(25±3)d后,犬的收缩末期和舒张末期左、右心房面积显著增大(与起搏前比较,P<0.01),左、右心房面积缩小分数显著减小(左心房:(35.7±1.9)%和(20.7±2.7)%,P<0.01;右心房:(35.0±2.3)%和(18.0±2.3)%,P<0.01),左室射血分数从(65.3±2.1)%降至(31.6±2.8)%(P<0.01)。实验组犬左、右心房有效不应期显著延长,心房内传导速率较对照组减慢。实验组有5只犬诱发出超过30 min的房颤,平均房颤持续时间较对照组显著延长(687±290)s和(13±9)s,P<0.01)。实验组平均房颤持续时间与左、右心房面积及面积缩小分数相关(P<0.05)。结论 快速心室起搏致心衰模型能稳定地诱发出房颤,房颤持续时间与心衰引起的显著心房结构和功能异常相关。     

Distribution of vasoactive intestinal polypeptide (VIP) binding in circular muscle and characterization of VIP binding in canine small intestinal mucosa.

The present study examined the localization and characterization of [125I]vasoactive intestinal polypeptide (VIP) binding to synaptosomes and enterocyte membranes using preparations made from homogenized canine intestinal mucosa and compared it to [3H]saxitoxin binding and VIP-immunoreactive content (markers for synaptosomes). The highest [125I]VIP binding was located in the P2 fraction and was correlated with the locations of maximal [3H]saxitoxin binding and VIP-immunoreactive content. This correlation indicates that VIP receptors are present on synaptosomes of canine small intestinal mucosa. A fraction enriched in synaptosomes contained a high density of saturable VIP receptors (352 +/- 26.40 fmol/mg) having high affinity (Kd, 0.23 nM) for [125I]VIP. Studies of association and dissociation of [125I]VIP to this site revealed that binding was fully reversible and yielded a Kd value similar to that from equilibrium binding. Competition binding experiments suggested the presence of two binding sites, a high and a low affinity binding site. The order of competition potency was VIP greater than peptide histidine isoleucine greater than secretin greater than peptide histidine methionine greater than or equal to [D-Ala4]VIP greater than or equal to [Phe1]VIP greater than VIP10-28 greater than [4-Cl-D-Phe6-Leu17]VIP. All these competitors displaced all specifically bound VIP. VIP, peptide histidine isoleucine and secretin interacted differentially with each of the two binding sites. Peptide histidine methionine, [D-Ala4]VIP, [Phe1]VIP, VIP10-28 and [4-Cl-D-Phe6-Leu17]VIP interacted with a single low affinity at all binding sites. Other VIP binding sites were sought in circular muscle and submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)     

正常关节软骨和骨关节炎关节软骨细胞中血管活性肠肽表达的比较

背景：神经肽的发现给骨关节炎的治疗带来了新的希望,但神经肽的表达与骨关节炎发病以及软骨退变程度的关系尚不清楚。目的：观察血管活性肠肽在正常关节软骨和不同退变程度骨关节炎软骨中的表达,以及血管活性肠肽表达与骨关节炎发病及软骨退变程度的关系。方法：选取2007-03/11中南大学湘雅医院骨科进行关节置换的骨关节炎患者的关节软骨标本26个,选取因外伤行截肢的膝关节软骨或股骨颈暴力骨折的股骨头正常关节软骨标本10个为对照,根据大体观察凿取正常和骨关节炎不同退变程度软骨块50个,再根据关节软骨改良Mankin病理评分法进行分组,采用免疫组织化学染色检测软骨组织中血管活性肠肽的表达和分布。结果与结论：各关节软骨中均可见到血管活性肠肽阳性神经纤维,正常关节软骨中血管活性肠肽的表达明显高于骨关节炎关节软骨（P〈0.05）。且血管活性肠肽表达与软骨改良Mankin病理评分呈负相关（r=-0.896,P〈0.05）。说明血管活性肠肽低表达与关节软骨退变程度、骨关节炎病程进展有关,可能是关节软骨退变、骨关节炎发病的机制之一。     

正常关节软骨和骨关节炎关节软骨细胞中血管活性肠肽表达的比较

背景:神经肽的发现给骨关节炎的治疗带来了新的希望,但神经肽的表达与骨关节炎发病以及软骨退变程度的关系尚不清楚。目的:观察血管活性肠肽在正常关节软骨和不同退变程度骨关节炎软骨中的表达,以及血管活性肠肽表达与骨关节炎发病及软骨退变程度的关系。方法:选取2007-03/11中南大学湘雅医院骨科进行关节置换的骨关节炎患者的关节软骨标本26个,选取因外伤行截肢的膝关节软骨或股骨颈暴力骨折的股骨头正常关节软骨标本10个为对照,根据大体观察凿取正常和骨关节炎不同退变程度软骨块50个,再根据关节软骨改良Mankin病理评分法进行分组,采用免疫组织化学染色检测软骨组织中血管活性肠肽的表达和分布。结果与结论:各关节软骨中均可见到血管活性肠肽阳性神经纤维,正常关节软骨中血管活性肠肽的表达明显高于骨关节炎关节软骨(P<0.05)。且血管活性肠肽表达与软骨改良Mankin病理评分呈负相关(r=-0.896,P<0.05)。说明血管活性肠肽低表达与关节软骨退变程度、骨关节炎病程进展有关,可能是关节软骨退变、骨关节炎发病的机制之一。     

Development of simplified vasoactive intestinal peptide analogs with receptor selectivity and stability for human vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors

Vasoactive intestinal peptide (VIP) is a widespread neurotransmitter whose physiological and pathophysiological actions are mediated by two receptor classes, VIP/pituitary adenylate cyclase-activating polypeptide (VPAC) 1 and VPAC2. VIP is a 28-amino acid peptide that is rapidly degraded and simplified; metabolically stable analogs are needed. In this study, we use information from studies of the VIP pharmacophore for VPAC1/VPAC2 to design nine simplified VIP analogs that could have high affinity and selectivity for each VPAC or that retained high affinity for both VPACs and were metabolically stable. From binding studies of their abilities to directly interact with hVPAC1 (T47D cells, hVPAC1-transfected cells) and hVPAC2 (Sup T1- and VPAC2-transfected cells) and to stimulate adenylate cyclase in each, two analogs [(Ala(2,8,9,11,19,22,24,25,27,28))VIP and (Ala(2,8,9,11,19,24-28))VIP] were found to have >2000- and >600-fold selectivity for hVPAC1. None of the nine analogs had hVPAC2 selectivity. However, two simplified analogs [(Ala(2,8,9,16,19,24))VIP and (Ala(2,8,9,16,19,24,25))VIP] retained high affinity and potency for both hVPACs. 125I-[Ala(2,8,9,16,19,24,25)]VIP was much more metabolically stable than 125I-VIP. The availability of these simplified analogs of VIP, which are metabolically stable and have either hVPAC1 selectivity or retain high affinity for both hVPACs, should be useful for exploring the role of VPAC subtypes in mediating VIPs' actions as well as being useful therapeutically and for exploring the usefulness of VIP receptor imaging of tumors and VIP receptor-mediated tumor cytotoxicity.     

Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis

The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6.0 pmol l-1 (range 0-20) in 112 normal subjects. In fifty-three patients with decreased kidney function plasma VIP was significantly increased (median 15.0 pmol l-1, range 0.5-70, P less than 0.0001) and positively correlated to serum creatinine concentration (r = 0.51, P less than 0.001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7.0 pmol l-1 range 0-86, P less than 0.01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P less than 0.05, n = 6) and in patients with cirrhosis (median 60%, P less than 0.02, n = 8), but not in uraemic patients (median 0%, NS n = 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (-42%, P less than 0.05, n = 6 and -45%, P less than 0.01, n = 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (-4%, NS, n = 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition.     

Radioimmunoassay of vasoactive intestinal polypeptide (VIP) in plasma.

A sensitive and specific radioimmunoassay for vasoactive intestinal polypeptide (VIP) has been developed, which can detect 3.3 pmol x L-1 of the peptide in plasma. Antisera to highly purified porcine VIP coupled to albumin were raised in eight rabbits. The final dilution, the avidity, and the specificity of each antiserum were determined. 125I-VIP served as label, and highly purified porcine VIP was used as standard. Separtation of antibody-bound and free VIP was achieved by plasma-coated charcoal. Nonspecific interference withe assay system was excluded by extraction of plasma samples with ethanol. The reliability of the assay was investigated by recovery experiments, by serial dilution of plasma samples with high concentration of endogenous VIP, and by immunosorption. The within-and between assay reproducibility at a concentration of 18.3 pmol x L-1 was 1.6 and 2.3 pmol x L-1 (1 S.D.), respectively. Median fasting concentration of VIP in plasma from 74 normal subjects was 7.3 pmol x L-1 (range: 0-20.0 pmol x L-1).     

肠易激综合征结肠黏膜P物质和血管活性肠肽变化的研究

背景脑肠肽作为一类具有神经递质和激素双重功能的小分子多肽,在肠易激综合征(IBS)的发病机制中起重要作用。目的探讨肠易激综合征(IBS)患者结肠黏膜P物质(SP)、血管活性肠肽(VIP)的变化及它们在IBS中的可能作用。方法对正常人18例、IBS腹泻型患者20例、便秘型患者22例各取回盲部、乙状结肠黏膜作SP、VIP免疫组织化学染色。结果IBS组患者肠黏膜SP、VIP免疫反应阳性神经纤维较正常对照组增多、增粗,强度增强(P<0.05)。结论IBS患者结肠粘膜SP、VIP水平与腹泻或便秘症状有一定的联系,SP、VIP可能参与IBS的病理生理过程。     

Plasma levels of substance P, neuropeptide Y and vasoactive intestinal polypeptide in patients with chronic tension-type headache

Animal and human studies have shown that substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) are involved in the pathophysiology of acute and chronic pain conditions. The primary aim of the present study was to compare plasma levels of SP, NPY and VIP in external jugular vein between patients with chronic tension-type headache and healthy controls. The secondary aim was to examine plasma levels of these neuropeptides in relation to headache state. In addition, we wanted to study the relation between cranial circulation (jugular vein) and peripheral circulation (antecubital vein). Blood from the external jugular and antecubital vein was drawn from 20 patients with chronic tension-type headache and 20 healthy controls. Plasma SP in patients, 2.0 (1.4-2.2) pmol/l, did not differ significantly from plasma SP in controls, 1.7 (1.1-2.1) pmol/l, (P=0.44). No significant differences were found between SP levels on days with headache, 1.5 (0.3-1.7) pmol/l, and SP levels on days without headache, 1.7 (1.1-1. 9) pmol/l, (P=0.06). Plasma NPY in patients, 118+/-3 pmol/l, did not differ significantly from plasma NPY in controls, 113+/-5 pmol/l, (P=0.40). There was no difference between NPY levels on days with headache, 120+/-3 pmol/l, and on days without headache, 118+/-3 pmol/l, (P=0.73). VIP levels in patients, 6 (4-7) pmol/l, did not differ significantly from VIP levels in controls, 5 (5-7) pmol/l, (P=0.50). No significant differences were found between VIP levels measured on days with headache, 5 (4-6) pmol/l, and VIP levels measured on days without headache, 6 (4-7) pmol/l, (P=0.81). Plasma levels of SP, NPY and VIP did not significantly differ between the peripheral and the cranial circulation neither in patients nor in controls (0.05). In summary, the present study indicates that plasma levels of SP, NPY and VIP are normal in chronic tension-type headache patients and largely unrelated to headache state.     

快速心室起搏诱导犬心力衰竭模型成功的时限观察

目的:观察快速心室起搏诱导犬心力衰竭模型的不同起搏时限对犬心功能、肾脏血流量的影响。方法:①实验于2004-03/2005-06在哈尔滨医科大学第一临床医学院实验外科完成。选用健康成年杂种家犬27只。随机分为3组:假手术组(n=6),起搏2周组(n=6),起搏4周组(n=7),起搏6周组(n=8)。②麻醉犬,左侧卧位,切开、悬吊心包,固定螺旋型心外膜起搏电极于右-室心尖部,连接实验用VOO型埋藏式起博器,于犬背部皮下造皮囊埋置起博器,恢复1周后起搏2,4,6周(起搏2,4,6周组),起搏频率均为240次/min;假手术组埋置起博器后不起搏。③采用彩色多普勒超声诊断仪测定各组犬左心室收缩末内径、左心室舒张末内径、左心室射血分数、心排血量、收缩期室间隔厚度、舒张期室间隔厚度、收缩期左心室后壁厚度、舒张期左心室后壁厚度。计算肾脏血浆流量(π×双肾动脉内径2×双肾动脉最大血流速度×0.57×60/4)。④组间计量资料差异比较采用单因素方差分析,两两比较用q检验,组内比较用配对t检验。结果:起搏6周组起搏期间死亡2只,最终进入结果分析:假手术组6只,起搏2,4,6周组分别6,7,6只。①起搏4和6周组犬心排血量、左室射血分数、肾脏血浆流量明显低于假手术组和起搏2周组(P<0.05～0.01),左心室收缩末内径、左心室舒张末内径明显大于假手术组和起搏2周组(P<0.05～0.01)。②起搏4和6周组犬收缩期室间隔厚度、舒张期室间隔厚度、收缩期左心室后壁厚度、舒张期左心室后壁厚度明显小于假手术组和起搏2周组(P<0.05～0.01)。起搏2周组犬收缩期左心室后壁厚度均明显小于假手术组(P<0.05)。结论:快速心室起搏所致的犬心力衰竭模型呈时间依赖性,起搏4周犬心功能、肾血流明显下降而生存率高。     

快速心室起搏诱导犬心力衰竭模型成功的时限观察

目的：观察快速心室起搏诱导犬心力衰竭模型的不同起搏时限对犬心功能、肾脏血流量的影响。 方法：①实验于2004—03／2005-06在哈尔滨医科大学第一临床医学院实验外科完成。选用健康成年杂种家犬27只。随机分为3组：假手术组（n=6），起搏2周组（n=6），起搏4周组（n=7），起搏6周组（n=8）。②麻醉犬，左侧卧位，切开、悬吊心包，固定螺旋型心外膜起搏电极于右一室心尖部，连接实验用V00型埋藏式起博器，于犬背部皮下造皮囊埋置起博器，恢复1周后起搏2，4，6周（起搏2，4，6周组），起搏频率均为240次／min；假手术组埋置起博器后不起搏。③采用彩色多普勒超声诊断仪测定各组犬左心室收缩末内径、左心室舒张末内径，左心室射血分数、心排血量、收缩期室间隔厚度、舒张期室间隔厚度、收缩期左心室后壁厚度、舒张期左心室后壁厚度。计算肾脏血浆流量（π&;#215;双肾动脉内径^2&;#215;双肾动脉最大血流速度&;#215;0．57&;#215;60／4）。④组间计量资料差异比较采用单因素方差分析，两两比较用q检验，组内比较用配对t检验。 结果：起搏6周组起搏期间死亡2只，最终进入结果分析：假手术组6只，起搏2，4，6周组分别6，7，6只。①起搏4和6周组犬心排血量、左室射血分数、肾脏血浆流量明显低于假手术组和起搏2周组（P〈0．05-0．01），左心室收缩末内径、左心室舒张末内径明显大于假手术组和起搏2周组（P〈0．05—0．01）。②起搏4和6周组犬收缩期室间隔厚度，舒张期室间隔厚度、收缩期左心室后壁厚度、舒张期左心室后壁厚度明显小于假手术组和起搏2周组（P〈0．05-0．01）。起搏2周组犬收缩期左心室后壁厚度均明显小于假手术组（P〈0．05）。 结论：快速心室起搏所致的犬心力衰竭模型呈时间依赖性，起搏4周犬心功能、肾血流明显下降而生存率高。     

Effect of vasoactive intestinal polypeptide on active and passive transport in the human jejunum.

The effect of intravenous vasoactive intestinal polypeptide (VIP) on normal transport mechanisms in the human jejunum in vivo was examined with the triple-lumen, steady-state perfusion technique. By using special test solutions that revealed different aspects of jejunal transport, we were able to evaluate the effect of VIP on specific transport processes, such as active bicarbonate absorption, active chloride secretion, and passive absorption or secretion of sodium chloride. At an infusion rate of 200 pmol/kg per h, VIP inhibited active bicarbonate absorption by approximately 42%, stimulated active chloride secretion to a slight extent, and slightly reduced passive sodium chloride absorption. A larger dose of VIP, 400 pmol/kg per h, had essentially the same effect on active bicarbonate absorption and active chloride secretion, but it markedly depressed passive sodium chloride absorption and also inhibited passive secretion induced by mannitol. VIP reduced the lumen-to-plasma unidirectional sodium and chloride flux rates, while the plasma-to-lumen flux rates were decreased to a lesser extent or remained unchanged. The potential difference became more lumen-negative with VIP, but the sodium diffusion and glucose-stimulated potential were not affected. We conclude that the major effect of VIP in the human jejunum is to decrease the normal absorption of water and electrolytes--not only active bicarbonate-mediated absorption, but also the passive absorption in response to osmotic forces generated by active or facilitated absorptive processes. Although an increase in chloride secretion does occur, this does not appear to be of major importance.     

Nutrition intervention to decrease symptoms in patients with advanced heart failure

For a majority of patients with advanced heart failure, there is a need for complementary, non‐pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients‐sodium, omega‐3 fatty acids, and lycopene‐can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6‐month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega‐3 fatty acids on heart failure symptoms, health‐related quality of life, and time to heart failure rehospitalization or all‐cause death. The aims of this double blind‐placebo controlled study are (1) to determine the effects of a 6‐month nutrition intervention on symptom burden (edema, shortness of air, and fatigue) and health‐related quality of life at 3 and 6 months, and time to heart failure rehospitalization or all‐cause death over 12 months from baseline; (2) compare dietary sodium intake, inflammation, and markers of oxidative stress between the nutrition intervention group and a placebo group at 3 and 6 months; and (3) compare body weight, serum lycopene, and erythrocyte omega‐3 index between the nutrition intervention group and a placebo group at 3 and 6 months. A total of 175 patients with advanced heart failure will be randomized to either the nutrition intervention or placebo group. © 2013 Wiley Periodicals, Inc. Res Nurs Health 36:120–145, 2013     

Preferential binding of vasoactive intestinal polypeptide to basolateral membrane of rat and rabbit enterocytes.

Binding of radioiodinated vasoactive intestinal polypeptide (VIP) to intestinal cell membranes of the rabbit ileum and rat jejunum was investigated. Specific binding of 125I-labeled VIP could be demonstrated only on the basolateral membrane and not on the brush border membrane. This corresponded with the lack of an effect on ion transport when VIP was applied to the mucosal side of an in vitro preparation of rabbit ileum. VIP altered ion transport only when it was applied to the serosal side. The binding of 125I-VIP was specific and dependent upon incubation temperature. There was a close correlation between the potency of VIP for inhibition of 125I-VIP binding and that for increasing adenylate cyclase activity. These observations demonstrate that VIP receptors are located on the basolateral membrane.     

Prolactin release induced by physical exercise is independent from peripheral vasoactive intestinal polypeptide secretion

The plasma concentrations of vasoactive intestinal polypeptide and prolactin were measured before and after an exhaustive and a submaximal exercise test in 7 male marathon runners. A significant increase of vasoactive intestinal polypeptide was recorded after both tests, whereas the prolactin increase was observed only after the exhaustive exercise test. No significant correlation was found between the plasma vasoactive intestinal polypeptide and the plasma prolactin values recorded during the two exercise tests. Data suggest that the exercise-induced prolactin release occurs independently from variations of the vasoactive intestinal polypeptide levels in peripheral circulation.     

胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系

目的探讨胆汁反流与食管下端括约肌组织中一氧化氮及血管活性肠肽的关系。方法对20名健康志愿者及86例反流性食管炎患者,进行食管压力测定、24h食管内pH、食管胆汁监测及食管下端括约肌组织中一氧化氮及血管活性肠肽含量检测;比较健康志愿者、酸反流者、胆汁反流者及混合反流者食管下端括约肌压力、一氧化氮及血管活性肠肽含量的变化。结果酸反流组、胆汁反流组及混合反流组一氧化氮及血管活性肠肽含量较健康志愿者组增多,而混合反流组较酸反流组、胆汁反流组增高(P<0.01);反流性食管炎患者食管下端括约肌压力与食管下端括约肌组织内的一氧化氮及血管活性肠肽呈负相关(r=-88.5,P<0.05和r=-89.9,P<0.05)。结论胆汁反流可导致食管粘膜炎症,食管下端括约肌局部组织中一氧化氮及血管活性肠肽明显增高,食管下端括约肌压力下降,胆汁与胃酸反流具有协同作用,加重食管粘膜损伤。     

Role of vasoactive intestinal polypeptide in the internal anal sphincter relaxation of the opossum.

The nature of the inhibitory neurotransmitter responsible for internal anal sphincter (IAS) relaxation in response to rectoanal reflex is not known. The objective of the present investigation was to examine the role of VIP in IAS relaxation in response to the rectoanal reflex in intact opossums with the use of VIP antagonists, [4CI-D-Phe6,Leu17] VIP and (N-AC-Tyr1,D-Phe2)-GRF (1-29)-NH2. Intraluminal pressures from the sphincter were monitored using low-compliance, continuously perfused catheters. VIP and the antagonists were administered close-intraarterially. The responses to VIP, rectoanal reflex, sacral nerve stimulation, and local intramural stimulation were examined before and after the VIP antagonists. The present studies in intact animals show: (a) VIP causes a dose-dependent fall in the IAS pressures by a direct action at the IAS smooth muscle; (b) VIP antagonists selectively and significantly antagonized the inhibitory action of VIP; and (c) VIP antagonists caused significant antagonism of the IAS relaxation caused by rectoanal reflex and the other neural stimuli. The antagonism of the IAS relaxation by the VIP antagonists, depending upon the volume of rectal distension used, ranged from 40% to 62% (P less than 0.05). From these results, we conclude that VIP acts as an inhibitory neurotransmitter for IAS relaxation during the rectoanal reflex.     

Absence of effect of secretin and cholecystokinin on plasma concentrations of vasoactive intestinal polypeptide and pancreatic glucagon

There is little information about the effect of peptides on the VIPergic system. Reports of the influence of secretin and cholecystokinin (CCK) on pancreatic alpha cells are contradictory. With the help of volunteers we investigated the influence of a new synthetic secretin (1 CU/kg/h, 0 to 120 min) alone and in combination with GIH-CCK (1 IU/kg/h, 60 to 120 min) on the concentrations of VIP (n = 13), pancreatic glucagon (PG) (n = 15) and blood sugar (n = 10). 6 of the volunteers were subjected to a randomized cross-over NaCl infusion study. Neither secretin (0 to 60 min) nor secretin and CCK (60 to 120 min) infusion caused a significant change in VIP (31 +/- 3 vs. 34 +/- 4.5 pg/ml, mean +/- SEM, p greater than 0.05), PG (102 +/- 9 vs. 116 +/- 12 vs. 114 +/- 12 pg/ml, p greater than 0.05) or blood sugar (about 90 mg/dl) concentrations. There is no evidence of an influence of secretin and CCK on te VIPergic system and the pancreatic alpha cells.