硝普钠对组胺所致离体豚鼠回肠H1效应的影响

目的 探讨一氧化氮(NO)与组胺（His）对离体豚鼠回肠生理活动的共同调节作用及其可能机理。方法 将离体回肠段固定于含95% O₂和5% CO₂台氏液恒温测试系统中（37℃），分别给予硝普钠（SNP，15、150、1500 μmol·L^-1）或SNP+硝苯地平（Nif，25、50、100 nmol·L^-1)，作用30 min， 再累积加入不同浓度的His(0.01～10 μmol·L^-1), 以平衡生理记录仪描记肠段收缩曲线,观察SNP和Nif对His引起的回肠H₁效应的影响。结果 ①SNP可增强低浓度His(0.01～0.1 μmol·L^-1)引起的回肠H₁效应，随His浓度增高，SNP的增强作用减弱；②去台氏液中外钙,有或无SNP存在时的His H₁效应均呈减弱作用，且两者间无显著差别；③Nif呈浓度依赖性地抑制His引起的H₁效应，并浓度依赖性地抑制SNP增强H₁效应的作用。结论 SNP可增强离体豚鼠回肠His H₁效应，该增强作用可能与回肠平滑肌细胞的外Ca²⁺内流有关。     

硝普钠在豚鼠离体气管螺旋条中的舒张作用

目的研究硝普钠(SNP)在豚鼠离体气管螺旋条中舒张作用的机制.方法在浴槽内加入硝普钠从10-7M至10-3M,观察气管螺旋条张力的变化,并检测浴槽中NO,气管螺旋条组织cAMP、cGMP的变化.结果加入硝普钠气管螺旋条张力下降,浴槽内NO增加,气管螺旋条组织cAMP、cGMP增加.结论硝普钠有舒张气管螺旋条的作用,推测是通过NO-cGMP系统发挥作用.     

硝普钠在豚鼠离体气管螺旋条中的舒张作用

目的:研究硝普钠(SNP) 在豚鼠离体气管螺旋条中舒张作用的机制.方法:在浴槽内加入硝普钠从10-7M至10-3M,观察气管螺旋条张力的变化,并检测浴槽中NO,气管螺旋条组织cAMP、cGMP的变化.结果:加入硝普钠气管螺旋条张力下降,浴槽内NO增加,气管螺旋条组织cAMP、cGMP增加.结论:硝普钠有舒张气管螺旋条的作用,推测是通过NO-cGMP系统发挥作用.     

硝普钠对增龄机体血小板功能影响的研究

目的探讨硝普钠对增龄机体血小板功能的影响。方法8mon、13mon Wistar大鼠,腹主动脉抗凝取血,分离富血小板血浆。使用硝普钠(SNP)前孵育血小板5min,然后用胶原诱导血小板活化。使用一氧化氮(NO)测定试剂盒测定不同年龄组动物血小板NO含量。利用Western blot方法分析VASP(vasodilator-stimulated phosphoprotein)磷酸化。使用6mon、36mon新西兰白兔颈总动脉取血分离血小板,测定血小板聚集。结果一氧化氮(nitric oxide,NO)的测定表明,硝普钠(sodium nitroprusside,SNP)处理的血小板以剂量依赖方式增加了血小板细胞内NO含量,在胶原诱导血小板活化的状态,13mon组大鼠血小板NO产生明显低于8mon组动物,两组之间差异有显著性(P<0.05)。VASP磷酸化结果显示8mon大鼠血小板的VASP磷酸化程度更强。血小板聚集实验显示3、10μmol.L-1SNP预处理6mon新西兰白兔血小板,聚集率分别为31%和4%。同样浓度SNP预处理36mon新西兰白兔的血小板,聚集率分别为88%和77%,两者之间差异有显著性。结论一氧化氮供体SNP具有增加血小板NO含量、抑制血小板功能的作用。SNP对血小板功能抑制的效果与年龄有相关性,高龄动物血小板NO产生以及VASP磷酸化程度降低,其分子机制可能与NO/cGMP通道的活性下降相关。这一结果为血栓研究提供了一个新的思路。     

硝普钠在豚鼠离体气管螺旋条中的舒张作用

目的：研究硝普钠（SNP）在豚鼠离体气管螺旋条中舒张作用的机制。方法：在浴槽内加入硝普钠从10^-7M至10^-3M,观察气管螺旋条张力的变化,并检测浴槽中NO,气管螺旋条组织cAMP、cGMP的变化。结果：加入硝普钠气管螺旋条张力下降,浴槽内NO增加,气管螺旋条组织cAMP、cGMP增加。结论：硝普钠有舒张气管螺旋条的作用,推测是通过NO-cGMP系统发挥作用。     

HPLC法测定硝普钠葡萄糖注射液中硝普钠的含量

目的建立高效液相色谱法（HPLC）测定硝普钠葡萄糖注射中硝普钠的含量。方法Di。mon。ilODSC18柱（250nm×4．6nm,5μm）;以0．34％硫酸氢四丁基铵与0．284％无水磷酸氢二钠溶液（用磷酸调pH值至6．0）-甲醇（50：50）为流动相;流速1．0mL／min;检测波长是254nm。结果硝普钠在9．96～637．44μg／ml范围内线性关系良好,平均回收率为99．8％,相对标准差（RSD）=0．3％。结论本法简便快捷,准确,可用于硝普钠葡萄糖注射中硝普钠的含量测定。     

HPLC法测定硝普钠氯化钠注射液中硝普钠的含量

目的：建立HPLC法测定硝普钠氯化钠注射液中硝普钠的含量。方法：Diamonsil ODS C18柱（250nm×4.6nm,5μm）;以0.34%硫酸氢四丁基铵与0.284%无水磷酸氢二钠溶液（用磷酸调pH值至6.0）-甲醇（50∶50）为流动相;流速1.0ml·min-1;检测波长是254nm。结果：硝普钠在9.96～637.44μg·ml-1范围内,（r=0.9998）线性关系良好,平均回收率为99.5%,RSD=0.8%（n=5）。结论：本法简便快捷,准确,可用于硝普钠氯化钠注射液中硝普钠的含量测定。     

硝普钠对离体视上核神经元谷氨酸反应的影响

目的观察一氧化氮(NO)供体硝普钠(sodiumnitroprusside,SNP)对视上核(supraopticnucleus,SON)神经元谷氨酸反应的影响,以了解NO对SON细胞活动的调制作用。方法对成年大鼠下丘脑冠状切片SON神经元进行细胞内生物电记录,测定其细胞电生理参数。结果对12个SON细胞局部压力喷射微量谷氨酸,均诱发伴有膜电阻减小的去极化反应,并呈剂量和膜电位依赖性特征。SNP在67%的细胞使谷氨酸反应幅度降低(P<0.05,n=8),时程缩短(P<0.01),而在33%的细胞延长谷氨酸反应时程(P<0.05,n=4)。结论SNP对SON神经元谷氨酸反应具有抑制和增强两种不同的调制作用,提示NO对SON神经元的兴奋性突触传递可能有双向性影响。     

硝普钠对离体视上核神经元的抑制和兴奋作用

目的观察NO供体硝普钠(SNP)对视上核(SON)神经元的影响,以了解NO对SON细胞活动的调节作用。方法对成年大鼠下丘脑切片SON神经元进行细胞内生物电记录,测定细胞电生理参数。结果在11个安静的细胞灌流给药SNP(1mmol·L-1)3～5min,使55％的细胞发生去极化(P＜0.05),伴有膜电阻和时间常数减小,而使45％的细胞超极化(P＜0.05)。SNP使73％细胞的诱发动作电位的幅度和超射值减小、半幅时程增大(P＜0.05),并伴放电频率降低、电流-电压曲线斜率减小、AHP幅度增大(P＜0.05);但在6个有自发性放电的细胞,SNP使67％细胞的自发性放电频率升高(P＜0.05)。结论SNP能细胞类型和功能状态依赖性地对SON神经元产生兴奋性或抑制性影响,提示NO对SON细胞活动有不同的调节作用。     

DDPH对多种介质所致豚鼠离体回肠收缩的影响

ＤＤＰＨ是根据抗心律失常药“美西律”的结构特点合成的新型化合物,其主要药理作用是降血压〔１〕。本文通过观察ＤＤＰＨ对磷酸组胺,Ａｃｈ,Ｃａ２＋致回肠收缩的影响,并比较Ｖｅｒ对高Ｋ＋所致回肠收缩的影响,以初步探讨ＤＤＰＨ对回肠平滑肌的作用及作用原理。１...     

Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum.

Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.     

庆大霉素对组胺所致豚鼠离体肠肌收缩的拮抗作用

目的观察庆大霉素对组胺所致豚鼠离体回肠的拮抗作用。方法离体豚鼠回肠经庆大霉素预处理后加入不同浓度组胺,记录肠肌收缩的幅度。结果发现庆大霉素能部分对抗组胺诱发的肠肌收缩,对组胺的减活指数为4.45,甚至对肠肌也有直接的舒张作用。结论庆大霉素对肠肌具有舒张作用,此作用在庆大霉素口服治疗感染性胃肠炎方面具有减轻症状的意义。     

Pharmacological characterization of histamine H3 receptors in human saphenous vein and guinea pig ileum

Studies were performed to assess the functional activity of histamine H3 receptors on neurogenic sympathetic end organ responses in cryopreserved human saphenous vein. (R)-alpha-methylhistamine inhibited electrical field stimulation-evoked contractile responses in a dose dependent manner (pD2 = 8.20). Prazosin (1 microM) and tetrodotoxin (1 microM) blocked the electrical field stimulation-evoked contractile responses in human saphenous vein indicating a sympathetic neural origin of these contractions. The histamine H3 antagonists thioperamide (pA2 = 8.41) and clobenpropit (pA2 = 10.10) produced parallel rightward shifts in the concentration response curve to (R)-alpha-methylhistamine in human saphenous vein and guinea pig ileum (pA2 = 8.59 and 9.83, respectively). Pretreatment with (R)-alpha-methylhistamine (1 microM) did not alter contractions to exogenous norepinephrine in human saphenous vein. In addition, clonidine (pD2 = 10.28) inhibited electrical field stimulation-evoked contractile responses in human saphenous vein which were blocked by yohimbine (30 nM, pA2 = 9.92) but did not alter the (R)-alpha-methylhistamine dose response curve. These results demonstrate the presence of functional presynaptic histamine H3 heteroreceptors on cryopreserved human saphenous vein sympathetic nerves that, upon activation, attenuate electrical field stimulation-evoked contractile responses in this vessel.     

Stimulative effect of sodium nitroprusside on peristaltic reflex in isolated guinea pig ileal segments.

Intestinal segments obtained from guinea pig ileum were set up in an organ bath to record peristaltic responses to distension by a pressure rise in the lumen. The effects of drugs applied in the bathing medium on the peristaltic responses were examined. Sodium nitroprusside (10(-9) M to 10(-5) M) stimulated the peristaltic reflex. Nitroglycerin (10(-7) M) was similarly effective in stimulating the peristalsis. A permeable cyclic GMP, 8-bromo cyclic GMP (2.5 x 10(-4) M), mimicked the action of these compounds. Methylene blue (10(-5) M) blocked the nitroprusside-induced stimulation of the peristalsis, but not the effect of 8-bromo cyclic GMP. Sodium nitroprusside did not change the baseline tension of the circular muscle, and it enhanced neither the contractile response to electrical direct stimulation nor the cholinergic transmission to the circular muscle. These results suggest that nitric oxide is formed from the nitrocompounds in mechanosensitive neurons in the intestine and causes activation of guanylate cyclase by which the level of intracellular cyclic GMP is elevated, and cyclic GMP acts to make the stretch receptors more sensitive. As nitric oxide is derived from the enteric vascular bed or neurons, its importance as a modulator of peristaltic activity in the intestine is discussed.     

扎普司特和谷胱甘肽翻转豚鼠离体气管对硝普钠的耐受性

上皮完整或去上皮的豚鼠离体气管以３００μｍｏｌ·Ｌ－１硝普钠（ＳＮＰ）预处理１ｈ，使ＳＮＰ对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移１．３－１．５倍，最大舒张率下降４１％－５８％，形成ＳＮＰ气管松弛作用的耐受性．８－溴环鸟苷酸可模拟ＳＮＰ在豚鼠离体气管形成的ＳＮＰ耐受性，谷胱甘肽（１ｍｍｏｌ·Ｌ－１）及环核苷酸磷酸二酯酶（ＰＤＥ）Ⅴ抑制剂扎普司特（３０μｍｏｌ·Ｌ－１）均可部分翻转ＳＮＰ的气管松弛作用耐受性，而蛋白合成抑制剂环己酰亚胺（１０μｍｏｌ·Ｌ－１）对ＳＮＰ的耐受性无预防作用．结果表明ＳＮＰ可产生豚鼠离体气管松弛耐受性，这可能是由于气管平滑肌中环鸟苷酸（ｃＧＭＰ）积聚而下调鸟苷酸环化酶（ＧＣ）活性和上调ＰＤＥⅤ活性．     

扎普司特和谷胱甘肽翻转豚鼠离体气管对硝普钠的耐受性

上皮完整或去上皮的豚鼠离体气管以300 μmol·L^-1硝普钠(SNP)预处理1 h,使SNP对抗乙醋甲胆碱气管收缩作用的剂量反应曲线右移1.3-1.5 倍, 最大舒张率下降41%-58%,形成SNP气管松弛作用的耐受性. 8-溴环鸟苷酸可模拟SNP在豚鼠离体气管形成的SNP耐受性, 谷胱甘肽(1 mmol·L^-1)及环核苷酸磷酸二酯酶(PDE) Ⅴ抑制剂扎普司特(30 μmol·L^-1)均可部分翻转SNP 的气管松弛作用耐受性,而蛋白合成抑制剂环己酰亚胺(10 μmol·L^-1)对SNP的耐受性无预防作用.结果表明SNP可产生豚鼠离体气管松弛耐受性, 这可能是由于气管平滑肌中环鸟苷酸(cGMP)积聚而下调鸟苷酸环化酶(GC)活性和上调PDEⅤ活性.     

Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum

The effects of azelastine on histamine- and leukotriene C4 and D4 (LTC4, LTD4)-induced contractile responses in isolated guinea pig ileum were investigated. Following a 2-min contact with the ileum, azelastine produced competitive antagonism of histamine (pA2 = 8.24). Following a 15-min contact, azelastine at 2.5 X 10(-9) M exerted competitive antagonism, but at higher concentrations (10, 40 and 160 X 10(-9) M) it not only shifted histamine concentration-effect curves to the right but also suppressed its maximum. Thus, azelastine exerts a dual (competitive/noncompetitive) antagonism of histamine depending upon the concentration and duration of contact. Azelastine and FPL 55712 (a known LT receptor antagonist) produced concentration-dependent antagonism of LTC4 and LTD4. Azelastine and compound FPL 55712 also exerted concentration-dependent reversal (relaxation) of pre-existing LTC4-induced contractions. In conclusion, the potent H1-histamine and leukotriene receptor blocking activities of azelastine may contribute to its antiasthmatic/antiallergic activities.     

Contractile effect of prolactin on guinea pig isolated ileum

Prolactin (PRL) at high concentrations contracted the guinea pig isolated ileum. The maximum response elicited by PRL was 44% of that of histamine-induced responses. There was no significant difference in potency between PRL preparations obtained from two different sources. PRL responses were nullified by denaturation or proteolytic digestion of the hormone. The contractile response was antagonised by atropine and potentiated by neostigmine, but unaffected by the prostaglandin antagonist SC-19220. The pA2 values of atropine against PRL and ACh were similar. Preincubation with morphine, which inhibits ACh release, produced slight inhibition of PRL-evoked contractions. Even high concentrations of PRL failed to produce any response in neostigmine-treated frog rectus muscle preparations. This suggests that PRL may produce contractions through a cholinergic mechanism involving muscarinic receptors. Enhanced gut motility reported earlier for hyperprolactinemic states may be attributed to this cholinomimetic effect of PRL on the intestinal tract.     

Characteristics of post-tetanic contraction induced by naloxone in guinea pig ileum

The characteristics of isolated guinea-pig ileal contractions of basal tension after tetanic stimulation in the presence of a high concentration of naloxone (NLX) [post-tetanic contraction] were investigated. The post-tetanic contraction did not occur in the absence of NLX, but did occur in a concentration-dependent manner in the presence of a high concentration of NLX (5 x 10(-7), 10(-6), 10(-5) and 5 x 10(-5) M), the concentration of which was higher than that required for antagonizing post-tetanic twitch inhibition. The contraction in the presence of 10(-6) M NLX was diminished by washing NLX from the preparation with Krebs-bicarbonate solution. The contraction under 10(-6) M NLX occurred in a frequency-dependent manner (5, 10 and 20 Hz), but not at 0.1 Hz. Tetanic stimulation (5, 10 and 20 Hz) without NLX did not induce this contraction. The post-tetanic contraction with 10(-6) M NLX had a tendency to be antagonized in the presence of 5 x 10(-6) M atropine. Methysergide (5 x 10(-5) M) had no effect on this contraction. Spantide (10(-5) M) largely inhibited the contraction, and indomethacin (5 x 10(-6) M) and tetrodotoxin (5 x 10(-7) M) completely inhibited this contraction. These results indicate that tetanic stimulation in the presence of a high concentration of NLX induces contraction of the ileal muscle due to the release of endogenous ileal contractile substances (substance P, prostaglandins and acetylcholine), and suggests that these contractions are closely linked to the endogenous opioid system induced by tetanic stimulation in the ileum.