急性氧乐果中毒脑AChE和ChAT免疫组化的实验研究

氧乐果是高毒类有机磷农药，被广泛应用于农业生产。有机磷农药的急性毒性作用主要归因于对胆碱能神经突触后膜上乙酰胆碱酯酶（AChE）的抑制，造成突触间隙神经递质乙酰胆碱（ACh）的堆积，后者持久地作用于ACh受体而引起一系列的胆碱能神经兴奋症状。ACh的水解酶和合成酶分别是AChE和胆碱乙酰转移酶（ChAT）。脑内AChE的抑制直接影响ACh的降解，在中枢神经系统的胆碱能损害中起着主要作用。而ChAT在急性有机磷中毒后的改变国内未见报道。本实验应用40％氧乐果制作家猫急性中毒模型。应用免疫组化的方法测定染毒前后猫脑组织中AChE和ChAT免疫阳性细胞面积比，为进一步研究急性有机磷农药中毒的作用机制提供实验依据。     

褪黑素对痴呆大鼠胆碱能功能的修复

目的　通过观察褪黑素对淀粉样 β多肽 2 5～ 35片段(Aβ2 5～ 3 5)所致学习记忆功能障碍大鼠海马胆碱乙酰转移酶(ChAT)和胆碱酯酶 (AChE)活性的影响 ,从而探讨Aβ和胆碱能系统在阿尔采末病 (AD)病理机制中的作用 ,以期为AD的有效治疗提供新的思路。方法　采用双侧海马内注射Aβ2 5～ 3 5诱导大鼠学习记忆功能障碍模型 ;用Moriss水迷宫法检测学习记忆功能 ;分别使用免疫组化和比色法检测ChAT和AChE的变化。结果　大鼠双侧海马内注射Aβ2 5～ 3 5(2 0 μg)可引起大鼠空间学习记忆功能障碍 ,ChAT免疫反应阳性神经元数量减少 ,且着色变淡 ;而脑组织中胆碱酯酶的活性改变不显著。褪黑素 (0 1、1、10mg·kg-1)连续给予 (ig) 10d ,对上述改变有不同程度的拮抗作用。 结论　褪黑素改善Aβ2 5～ 3 5诱导的大鼠学习记忆功能障碍可能与其改善胆碱能系统的功能有关     

胆碱乙酰基转移酶对老年性痴呆模型小鼠学习记忆的影响

早老性痴呆（阿尔茨默氏病，Alzheimer＇sdisease．AD）是一种以认知障碍和记忆力损害为特征的胆碱能神经进行性退行性疾病。从源头上补充胆碱能神经递质乙酰胆碱的合成酶胆碱乙酰基转移酶（choline—O—acetyltransferase，ChAT），应能增强胆碱能神经功能。首先人源性重组ChAT融合蛋白基因进行构建、克隆及表达，重组ChAT静脉注射给小鼠后能穿越血脑屏障并在中枢催化合成乙酰胆碱。重组ChAT静脉给予自然衰老认知障碍模型小鼠后，能显地改善痴呆症状。     

广西圆斑蝰蛇毒中提取的NGF对Aβ25-35诱导的AD模型小鼠脑乙酰胆碱及其代谢酶含量的影响

目的观察广西圆斑蝰蛇毒中提取的NGF对Aβ25-35诱导的AD模型小鼠胆碱能神经系统的影响。方法采用脑立体定位仪自侧脑室注射Aβ25-35建立AD小鼠模型,分别给予不同剂量NGF对AD小鼠进行治疗,测定不同实验组小鼠脑组织乙酰胆碱（Ach）含量变化及乙酰胆碱脂酶（AchE）和胆碱乙酰转移酶（ChAT）活性变化。结果广西圆斑蝰蛇毒NGF呈剂量依赖性的对AD小鼠脑内胆碱能系统产生调节作用。与模型组比较,NGF中剂量组（0.4μg·μL^-1与高剂量组（0.56μg·μL^-1小鼠脑组织AchE活性均有显著降低（P〈0.05,P〈0.01）,且各剂量组间呈逐渐下降的趋势;各剂量组（0.28,0.40,0.56μg·μL^-1小鼠脑组织Ach含量均显著增加（P〈0.05）,其中高剂量组（0.56μg·μL^-1ChAT活性明显升高（P〈0.05）,且各剂量组间这两个指标均呈逐渐上升的趋势。结论广西圆斑蝰蛇毒NGF可促进ChAT的表达,增加Ach的合成;降低脑组织AchE的活性,抑制Ach分解,增加脑内Ach含量,改善AD模型小鼠的学习、记忆障碍。     

知母皂苷元对拟痴呆大鼠β-淀粉样肽沉积及胆碱能系统功能的影响

目的　观察知母皂苷元 (ZMS)对拟痴呆大鼠模型脑内 β 淀粉样肽沉积及胆碱能系统功能的作用。 方法　单侧基底核内联合注射 β 淀粉样肽2 5-3 5片段 (β AP2 5-3 5)和兴奋性氨基酸建立大鼠拟痴呆模型 ,然后将模型动物分为假手术组 37、模型组和ZMS组 ,采用免疫组织化学方法和图像分析法测定β AP2 5-3 5沉积斑块的面积。用避暗法及跳台法测定动物的学习记忆功能 ,用放射配基结合分析法分别测定脑胆碱乙酰转移酶 (ChAT)活性和M受体密度。结果　一次性脑内联合注射 β AP +IBO后 ,模型大鼠脑内有明显的 β AP斑块沉积 ,而模型大鼠喂服ZMS 6 0d后 ,能有效地减少β AP沉积的面积 ,同时ZMS能明显改善模型动物的学习记忆功能 ,并提高模型动物脑内ChAT活性和M受体密度。结论　ZMS可能对脑内 β AP的沉积有一定的清除作用 ,并对AD低下的胆碱能系统功能有一定的改善和治疗作用     

知母皂苷元对拟痴呆大鼠β-淀粉样肽沉积及胆碱能系统功能的影响

目的　观察知母皂苷元 (ZMS)对拟痴呆大鼠模型脑内 β 淀粉样肽沉积及胆碱能系统功能的作用。 方法　单侧基底核内联合注射 β 淀粉样肽2 5-3 5片段 (β AP2 5-3 5)和兴奋性氨基酸建立大鼠拟痴呆模型 ,然后将模型动物分为假手术组 37、模型组和ZMS组 ,采用免疫组织化学方法和图像分析法测定β AP2 5-3 5沉积斑块的面积。用避暗法及跳台法测定动物的学习记忆功能 ,用放射配基结合分析法分别测定脑胆碱乙酰转移酶 (ChAT)活性和M受体密度。结果　一次性脑内联合注射 β AP +IBO后 ,模型大鼠脑内有明显的 β AP斑块沉积 ,而模型大鼠喂服ZMS 6 0d后 ,能有效地减少β AP沉积的面积 ,同时ZMS能明显改善模型动物的学习记忆功能 ,并提高模型动物脑内ChAT活性和M受体密度。结论　ZMS可能对脑内 β AP的沉积有一定的清除作用 ,并对AD低下的胆碱能系统功能有一定的改善和治疗作用     

淫羊藿苷对淀粉样β蛋白片段25-35所致大鼠学习记忆障碍的改善作用

目的观察淫羊藿苷对淀粉样β蛋白片段25-35(Aβ25-35)所致阿尔茨海默病(AD)模型大鼠学习记忆能力的保护作用,并探讨其可能的作用机制。方法Wistar雄性大鼠,右侧海马内注射Aβ25-3510μg制备AD模型,次日起淫羊藿苷30,60和120mg.kg-1灌胃给药,连续14d,d15～19Morris水迷宫检测大鼠空间辨别学习记忆能力;d20检测海马组织中谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)及一氧化氮合酶(NOS)的活性,免疫组化法检测海马内乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的表达。结果与模型对照组比较,淫羊藿苷给药14d明显改善大鼠学习记忆能力;海马组织中SOD和GSH-PX活性升高,NOS活性降低;海马内AChE及ChAT的表达增加。结论淫羊藿苷可以改善Aβ25-35海马内注射所致AD模型大鼠的学习记忆能力,其作用可能与其增加AChE和ChAT表达,增强SOD和GSH-PX等自由基清除酶活性,降低NOS活性,减少NO释放等多种机制,促进胆碱能递质系统功能的恢复有关。     

恒河猴大脑注射Aβ1-42 和Thiorphan对胆碱能神经元影响的研究

目的 观察颅内灌注Aβ1-42和Thiorphan给药后恒河猴基底、核大脑皮质等部位胆碱能神经元的改变.方法 将恒河猴4只,分为对照组(1只)与实验组(3只),对照组开颅后只注射0.9%氯化钠溶液,实验组开颅后先注射Thiorphan到猕猴的基底核和大脑皮质消耗已存在的Neprilysin,然后再缓慢的注射孵育好的纤丝状Aβ1-42,再植入含有Thiorphan的微渗透泵到基底核.免疫组织化学方法检测大脑切片胆碱乙酰转移酶(ChAT)免疫反应活性及阳性神经元数量及形态学改变.结果 给药后实验组恒河猴基底核、皮质等部位的胆碱能神经元数量减少和ChAT水平降低.结论 Aβ1-42和Thiorphan联合颅内给药后损害大脑基底核、皮质等部位的胆碱能神经元.     

复智散对阿尔采末病模型小鼠治疗作用的研究

目的观察复智散(FZS)对Aβ25-35诱导的阿尔采末病(AD)模型小鼠的治疗作用。方法Aβ25-35侧脑室注射制作AD小鼠模型,以不同剂量的FZS灌胃治疗,通过Morris水迷宫和小鼠穿梭程序自动控制仪检测小鼠的认知功能,采用比色法测定小鼠脑内胆碱乙酰基转移酶(ChAT)、乙酰胆碱酯酶(AChE)活性及乙酰胆碱(ACh)含量。结果不同剂量的FZS不仅对AD小鼠的认知功能有明显的改善作用,且能增加AD小鼠脑内的ChAT活性及ACh含量,并降低AChE活性。结论FZS在1.25~10g·kg-1剂量范围内均有治疗小鼠AD的作用,但用1.25g·kg-1剂量时治疗效果最佳。     

银杏内酯对拟AD模型大鼠空间学习记忆能力和脑内ChAT表达的影响

目的探讨银杏内酯对拟AD大鼠学习记忆能力影响的可能机制。方法大鼠海马OA(Okadaic acid)微量注射,银杏内酯灌胃。水迷宫实验检测大鼠学习记忆能力;West-ern blot实验检测大鼠海马烟碱型胆碱能受体的表达;免疫组化观察大鼠脑内ChAT的表达。结果与对照组比较,模型组大鼠学习记忆能力明显下降(P<0.01),烟碱型胆碱能受体表达减少(P<0.05),ChAT免疫阳性神经元减少(P<0.05)。与模型组相比,银杏内酯组大鼠学习记忆能力明显提高(P<0.01),烟碱型胆碱能受体表达增多(P<0.05),ChAT免疫阳性神经元增多(P<0.05)。结论银杏内酯提高拟AD大鼠的学习记忆能力可能与其改善模型鼠胆碱能系统的功能有关。     

VIP-ergic and cholinergic innervations in internal carotid arteries of the cat and rat.

Using immunohistochemical methods, choline acetyltransferase and vasoactive intestinal polypeptide immunoreactive (ChAT-I and VIP-I) fine fibers with varicosity-like structures were observed in the rat and cat cerebral arteries. Acetylcholine (ACh) induced dual responses in endothelium-intact internal carotid arteries of the cat; it induced vasodilation at low concentrations and constrictions at high concentrations (greater than 10(-6) M). ACh induced contraction exclusively in endothelium-rubbed preparations. Atropine (10(-7) M) blocked ACh-induced constriction and dilatation. ACh-induced vasodilation was potentiated by M & B 22,948 (2 x 10(-5) M), a selective cyclic GMP phosphodiesterase inhibitor. Vasoconstriction induced by ACh was inhibited by neomycin (3 x 10(-3) M), an inositol phosphate synthesis inhibitor, which did not affect the neuropeptide Y-induced contraction. VIP-induced dilation of the cat internal carotid arteries was not affected by removing the endothelial layer, but was blocked by VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) and potentiated by cilostazol (2 x 10(-5) M), a selective cyclic AMP phosphodiesterase inhibitor. These results are consistent with previous findings that cerebral blood vessels receive cholinergic and VIP-ergic innervations, and that ACh-induced endothelium-dependent vasodilation is mediated by cyclic GMP synthesis, and that VIP-induced endothelium-independent vasodilation is mediated by cyclic AMP synthesis. The present study, however, demonstrates for the first time the presence of varicosity-like structure associated with ChAT-I fibers, suggesting the presence of cholinergic nerve terminals and that ACh-induced cerebral vasoconstriction is mediated by phosphatidyl-inositide turnover.     

Different role of nitric oxide and endothelium-derived hyperpolarizing factor in endothelium-dependent hyperpolarization and relaxation in porcine coronary arterial and venous system

OBJECTIVE: We compared the basal and bradykinin (BK)-induced NO release and endothelium-derived hyperpolarizing factor-mediated function between coronary arteries and cardiac veins. METHODS AND RESULTS: Isolated coronary vessels (large arteries, cardiac veins as well as microvessels) were studied. An NO-specific electrode and a conventional intracellular glass microelectrode were used to directly measure NO released from endothelial cells and hyperpolarization of smooth muscle cells in conduit coronary vessels. The basal and BK-induced release of NO was 14.2 +/- 2.0 nmol/L and 237.1 +/- 27.2 nmol/L (n = 8) in the artery, significantly greater than in veins (8.0 +/- 1.1 nmol/L and 135.6 +/- 14.5 nmol/L, n = 8, P < 0.01). The BK-induced hyperpolarization was significantly reduced by N-nitro-L-arginine, indomethacin, and hemoglobin in both arteries and veins and was greater in the arteries. The EDHF-mediated relaxation was significantly higher in the arteries than in veins, greater in microveins than in large veins, and almost abolished by charybdotoxin and apamin. CONCLUSIONS: Both NO and EDHF are involved in the regulation of the vascular tone in the coronary arterial and venous systems but the amount of NO release and the EDHF-mediated relaxation and associated hyperpolarization are less significant in the vein than in the artery in the coronary system.     

NEUROPEPTIDE Y INDUCES AND MODULATES VASOCONSTRICTION IN INTRACRANIAL AND PERIPHERAL VESSELS OF ANIMALS AND MAN

• 1 Neuropeptide Y (NPY) has recently been reported to coexist with noradrenaline (NA) in central as well as peripheral noradrenergic nerves. NPY-containing nerve fibres are particularly numerous around blood vessels.
• 2 Studies were performed on isolated pial arteries as well as on arteries and veins from several peripheral vascular beds from rabbit, cat and man. NPY induced a varying degree of direct contraction of the vessels with an E_Am up to 15 mN. Pial arteries were more sensitive than peripheral arteries to NPY (mean EC₅₀ = 7.6 × 10^?9 M). The presence of NPY did not cause any consistent or significant potentiation of the contractile response to NA in any of the vessels tested.
• 3 Transmural electrical stimulation of the perivascular nerves (including blockade with tetrodotoxin) was performed mainly with auricular artery from the rabbit. Blocking experiments confirmed that the neurogenic contraction was mediated by noradrenergic-type fibres. NPY caused a concentration-related potentiation of the neurally evoked contractile response. The peptide also potentiated the tetrodotoxin-resistant probably non-neurogenic contractions obtained during enhanced electrical field stimulation.
• 4 It is concluded that NPY interacts with NA during sympathetic nerve activation primarily through a presynaptic effect.

     

Some Embryological Aspects of Cholinergic Innervation in the Cardiovascular System — A Close Association With the Subintestinal Circulatory Channel

A series of our studies on the dog venous system revealed that cholinergic excitatory innervation was localized in a group of veins: the portal, mesenteric, and hepatic veins and the middle segment of the inferior vena cava. Our studies on pharmacological responsiveness of dog veins also revealed that they could be divided into two groups: the visceral and somatic parts, and the cholinergic excitatory innervation localized to the visceral part. Considering these results and some relevant literature, a hypothesis is proposed on the classification of muscles of the cardiovascular system and some embryological aspects of the parasympathetic cholinergic innervation in the circulatory system are discussed. The embryonic circulatory system of vertebrates can be divided into two parts: somatic and visceral. The body of an embryo is regarded as a double tube and vessels of the visceral part and the heart belong to the inner tube. The muscle of these vessels and the heart are derived from visceral mesoderm, either the coelomic epithelium or mesenchymal cells, in common with muscle of the digestive tube; and thus the parasympathetic cholinergic nerves innervating the muscle of the digestive tube also distribute to these vessels and the heart. The heart and vascular muscles in the visceral part are structures developed early in the course of evolution in invertebrates. Their primary function is to propel the body fluid, and the chief structure containing them is the subintestinal circulatory channel (ventral aorta ? heart ? subintestinal vein). They exhibit spontaneous, rhythmic activity, showing characteristics of a single unit muscle, and receive parasympathetic cholinergic innervation. On the other hand, the vascular muscles in the somatic part are endothelium-associated muscles developed anew in the vertebrate; do not contract spontaneously, being classified as a multiunit muscle; and lack parasympathetic cholinergic innervation.     

CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells.

Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. Immunohistochemistry revealed that CYP1A1 was preferentially induced in endothelial cells (EC) in the choroid plexus, in veins in the leptomeninges, and in cerebral veins of AhR agonist-pretreated mice. No induction occurred in cerebral capillary EC. In vehicle-treated mice no localization of CYP1A1 in EC was observed. CYP1B1 was expressed in smooth muscle cells of arteries in the leptomeninges, in cerebral arteries/arterioles and to a low extent in ependymal cells of AhR agonist- and vehicle-treated mice. No CYP1B1 was detected in capillary loops of the choroid plexus or in cerebral capillaries. Following administration of [(3)H]DMBA to BNF-pretreated mice, a marked irreversible binding in EC of the choroid plexus and of veins in the leptomeninges was observed but not in cerebral capillaries. In vehicle-treated mice, there was no [(3)H]DMBA-binding at these sites. Furthermore, a high level of irreversibly bound [(3)H]DMBA occurred in EC at these sites in precision-cut mouse/rat brain slices and in excised blood-brain interfaces incubated with [(3)H]DMBA. Since [(3)H]DMBA binding sites corresponded with the sites of CYP1A1 induction, we conclude that rodents express a constitutively low but highly inducible and functional CYP1A1 in EC of some of the blood-brain interfaces. The role of CYP1A1/1B1 and environmental pollutants in the etiology of cerebrovascular disease needs further consideration.     

Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 microg/m(3) for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS.     

The anatomy and physiology of the bronchial circulation.

The origin and distribution of the bronchial vasculature vary considerably between and among species both at the macro- and microvascular level. Bronchial vessels usually originate from the aorta or intercostal arteries, entering the lung at the hilum, branching at the mainstem bronchus to supply the lower trachea, extrapulmonary airways, and supporting structures; this fraction of the bronchial vasculature drains into the right heart via systemic veins. Bronchial vessels also supply the intrapulmonary airways as far as the level of the terminal bronchioles where they form extensive anastomoses with the pulmonary vasculature; this systemic-to-pulmonary blood drains via pulmonary veins to the left heart. Repeated arborization of the bronchial artery along the length of the tracheal bronchial tree results in a vast increase in the total surface area of the vascular bed. The tracheal bronchial vasculature consists of a continuous dense network of subepithelial capillaries that converge to form venules extending to a deeper plexus of larger venules and arterioles on the adventitial side of the smooth muscle. Innervation is under the control of vasodilatory parasympathetic nerves that release acetylcholine and vasoactive intestinal polypeptide; vasoconstrictor sympathetic nerves that release norepinephrine and neuropeptide Y; and sensory nerves that release substance P, neurokinin A, and calcitonin gene-related peptide, all of which are vasodilators. Mechanical factors such as the downstream pressure and alveolar pressure also influence the distribution of blood flow through the tracheal bronchial vasculature.     

Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum

1. In normal mice, the distribution of adrenergic, cholinergic, some peptidergic, and neuronal nitric oxide synthase (nNOS)-containing nerves were investigated. Functional in vitro correlates were obtained. An in vivo model was developed in which erectile haemodynamics in response to drugs or nerve-stimulation were studied. 2. Immunoreactivities for vesicular acetylcholine transporter protein (VAChT), nNOS-, and vasoactive intestinal polypeptide (VIP), co-existed in nerve fibres and terminal varicosities. Immunoreactivities for neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were found in the same nerve structures. 3. Chemical sympathectomy abolished TH- and NPY-IR nerve structures in cavernous smooth muscle bundles. The distribution of calcitonin gene-related peptide (CGRP)-, nNOS-, VAChT- and VIP-IR nerve structures was unchanged. 4. In endothelial cells of the central and helicine arteries, veins and venules, intense immunoreactivity for endothelial NOS (eNOS) was observed. No distinct eNOS-IR cells were found lining the cavernous sinusoids. 5. In vitro, nerve-induced relaxations were verified, and endothelial NO/cyclic GMP-mediated relaxant responses were established. VIP and CGRP had small relaxant effects. A functioning adenylate cyclase/cyclic AMP pathway was confirmed. 6. Neuronal excitatory responses were abolished by prazosin, or forskolin. VIP and CGRP counteracted contractions, whereas NPY and scopolamine enhanced excitatory responses. 7. In vivo, erectile responses were significantly attenuated by L-NAME (50 mg kg(-1)) and facilitated by sildenafil (200 microg kg(-1)). 8. It is concluded that the mouse is a suitable model for studies of erectile mechanisms in vitro and in vivo.     

5-HT1B-receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan

AIMS: 5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution of 5-HT1B-receptor immunoreactivity (i.r.) in human blood vessels (including target and nontarget vessels) and confirmed the functionality of this receptor protein, by comparing the vasoconstrictor effects of sumatriptan and 5-HT (the endogenous ligand) in isolated vessels. METHODS: Blood vessels (middle meningeal, pial, temporal and uterine arteries and saphenous veins) were obtained from surgical patients (with consent). Sections of the vessels were prepared for routine immunohistochemical studies using specific 5-HT1B- and 5-HT1D-receptor antibodies. For functional studies, ring segments of the vessels were mounted in organ baths for isometric tension recording. RESULTS: 5-HT1B-receptor i.r. was detected on the smooth muscle layer in middle meningeal, pial and uterine arteries and in saphenous vein and sumatriptan produced contractions in these vessels with potency values (mean pEC50) of 7.00, 7.08, 6.44 and 6.61, respectively, the magnitude of contraction was greatest in the cranial arteries with Emax values of 100.7, 60.3, 23.0 and 35.9%, respectively (expressed as a percentage of the reference agonist 45 mm KCl). 5-HT1B-receptor i.r. was not detected in temporal artery and sumatriptan had no effect in this artery. 5-HT1D-receptor i.r. was not detected in any of the vessels studied. CONCLUSIONS: Sumatriptan can evoke vasoconstriction in antimigraine target vessels and also in nontarget vessels through an action at 5-HT1B-rcceptors. Sumatriptan acts preferentially to cause contraction in human cranial arteries compared with the other blood vessels we examined and this effect is likely to be shared by other drugs of this class.     

Pharmacology of pentoxifylline in isolated canine arteries and veins

Pentoxifylline possesses vasodilator properties, but little information is available on the mechanism of action explaining this vasodilator effect. The present experiments were designed to determine the effects of the compound on vascular smooth muscle, endothelium, and adrenergic nerves in rings of isolated canine blood vessels. Pentoxifylline did not affect basal tension in coronary and femoral arteries or in saphenous and mesenteric veins; it did not alter the rhythmic activity of the latter, but did cause endothelium-independent relaxations of unstimulated basilar arteries. In coronary arteries and saphenous veins, but not femoral arteries contracted with prostaglandin F2 alpha, the compound caused relaxations which were not affected by propranolol or by removal of the endothelium. Pentoxifylline inhibited the endothelium-dependent contractions to the Ca2(+)-ionophore A23187 in the basilar artery. In saphenous veins (with endothelium), pentoxifylline did not inhibit responses to high K+, electrical stimulation of the adrenergic nerves, or exogenous norepinephrine (NE); it reduced contractions evoked by xylazine and hypoxia. In the basilar artery and the saphenous vein, the inhibitory effect of pentoxifylline was prevented by inhibitors of cyclooxygenase and thromboxane synthetase. These experiments suggest that the dilator properties of pentoxifylline in isolated canine blood vessels are primarily at the level of the vascular smooth muscle and may involve decreased production of, or reduced responsiveness to, endogenous thromboxanes.