Hypotensive shock and angio-oedema from angiotensin II receptor blocker: a class effect in spite of tripled tryptase values

In adverse reactions with shock, tripled tryptase values can support a diagnosis of anaphylaxis. A 51-year old physically fit woman experienced angio-oedema and hypotensive shock after irbesartan ingestion requiring noradrenaline infusion. Serum tryptase rose to three times the normal value. Total immunoglobulin E and skin prick tests were normal, however. As nonallergic increases in tryptase have been observed, e.g. during angio-oedema from angiotensin-converting enzyme inhibitors, and bradykinin itself can degranulate mast cells acutely, we interpret the reaction as a class effect. To our knowledge, our report is one of the first on shock and angio-oedema from irbesartan.     

PARTICIPATION OF PROSTANOIDS IN CHEMICAL ACTIVATION OF THE PERICARDIAL PRESSOR REFLEX IN DOGS

1. Experiments were performed on anaesthetized, open-chest dogs to determine the reflex effects on systemic blood pressure and heart rate produced by stimulation of the parietal pericardium with bradykinin, prostacyclin, prostaglandin E₂ (PGE₂), prostaglandin D₂ (PGD₂) and arachidonic acid. 2. Pericardial application of bradykinin (1 μg) consistently elicited reflex increases in blood pressure and heart rate, whereas application of prostanoids or arachidonic acid in doses up to 10 μg failed to produce any cardiovascular responses. 3. Indomethacin, applied either directly to the parietal pericardium (1 μg/ml) or given intravenously (5 mg/kg) caused a long lasting reduction of the reflex responses to bradykinin. The reflex effects of bradykinin could be temporarily restored by treatment of the pericardium with either prostacyclin (0.1 μg/min) or PGE₂ (0.1 μg/min). PGD₂ (0.1-1 μg/min) did not influence the bradykinin induced pericardial reflex. 4. Superfusion of arachidonic acid (3 μg/min) over the pericardium amplified the reflex effects of bradykinin when given before, but not when given after indomethacin treatment. 5. The results indicate that locally formed prostanoids, specifically prostacyclin and PGE₂, can facilitate activation of the pericardial pressor reflex by bradykinin. The findings may be relevant to the changes in cardiovascular activity occurring during pericardial inflammation.     

Modulation of allergic and immune complex-induced lung inflammation by bradykinin receptor antagonists

Objective: The effect of bradykinin (B₁ or B₂) receptor antagonists was studied in allergic and immune-complex-induced lung inflammation.Methods: Lungs of BALB/c mice were examined 24 h after induction of lung inflammation, either allergic (ovalbumin-sensitized submitted to two aerosol of antigen, one week apart) or immune-complex induced (intratracheal instillation of IgG antibodies followed by intravenous antigen). The bradykinin B₂ receptor antagonist, HOE-140 or bradykinin B₁ receptor antagonist, R-954 were given intraperitoneally (100 g/kg), 30 min before induction.Results: In allergic inflammation, pre-treatment with R-954 reduced eosinophil infiltration into the lungs, mucus secretion and the airway hyperreactivity to methacholine. Pre-treatment with HOE-140 increased eosinophil infiltration but did not affect the other parameters. In immune-complex inflammation, HOE-140 increased neutrophil infiltration but not their activation nor the hemorrhagic lesions. R-594 pre-treatment did not change the parameters examined.Conclusion: These results show important modulatory effects of bradykinin B₁ and B₂ receptor antagonists in both models of lung inflammation.Received 6 May 2003; returned for revision 22 July 2003; accepted by N. Boughton-Smith 8 October 2003Received 6 May 2003; returned for revision 22 July 2003; accepted by N. Boughton-Smith 8 October 2003     

链佐星所致糖尿病大鼠主动脉内皮依赖舒张反应损伤的特征(英文)

目的:研究早期糖尿病大鼠内皮依赖舒张反应(EDR)损伤的机制。方法:离体主动脉环张力实验。结果:乙酰胆碱(ACh),组胺(His),缓激肽,环匹阿尼酸(CPA)在糖尿病组EDR均比对照组明显减弱。而卡西霉素诱导的EDR未见损伤。L-NAME(0.3mmol·L~(-1))预处理取消所有EDR,并使两组间效应均一化。ACh或CPA诱导最大EDR时,卡西霉素(1μmol·L~(-1))进一步扩张糖尿病而非正常组血管环。硝普钠扩血管及CPA或His缩血管效应均无组间差异。结论:在4周链佐星糖尿病大鼠主动脉,受体而不是非受体介导的EDR普遍损伤,其机制与内皮细胞电容性钙内流信号通路受损从而使NO合成减少有关。     

Interaction between bradykinin,morphine, and naloxone at the sensomotor cortical unit level

The effects of bradykinin, morphine, and naloxone applied by microiontophoresis on sensomotor cortical neurons were studied in waking rabbits. Bradykinin increased the discharge frequency of most neurons. Morphine inhibited unit activity. Against the background of morphine, bradykinin had no activating action. Naloxone abolished the depriming effect of morphine and restored the response of the neurons to bradykinin. It is concluded that bradykinin interacts with opiate receptors in the brain.Laboratory of Molecular Neurophysiology and Biochemistry, P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 683–685, December, 1979.     

银杏叶提取物对缓激肽诱导的大鼠记忆能力减退的改善作用

目的观察银杏叶提取物(GBE)对缓激肽诱导的大鼠记忆能力减退的改善作用,并探索其作用机制。方法大鼠经Morris水迷宫训练合格后,分别灌胃给予GBE(40,80和160mg.kg-1,每日1次)3周,于给药1周时海马内注射20mmol.L-1缓激肽5μL,给药结束后用Morris水迷宫检测大鼠的空间记忆能力,RT-PCR法测定海马半胱氨酸天冬氨酸蛋白酶(caspase)3及caspase8mRNA的表达。结果海马内注射缓激肽后,大鼠在水迷宫中的逃避潜伏期和寻台搜索距离明显延长,且海马caspase3和caspase8mRNA表达增加;GBE对缓激肽诱导的空间记忆能力减退有改善作用,且降低海马caspase3及caspase8mRNA表达。结论GBE可改善缓激肽诱导的大鼠记忆能力减退,其机制可能与降低海马caspase3和caspase8mRNA表达有关。     

缓激肽在缺血预处理中的作用

目的 :研究缓激肽 (BK)是否参与了大鼠心肌缺血预处理 (IP)。方法 :观察缺血再灌注组、缺血预处理组、缺血再灌注前给予缓激肽组、缺血再灌注前给予缓激肽及缓激肽B2 受体拮抗剂B1650 组以及缺血预处理时加B1650 组各组缺血复灌前后心功能变化 ,并且检测复灌末丙二醛 (MDA)和超氧化物歧化酶 (SOD)的变化。结果 :缺血再灌注前给予缓激肽可明显减轻再灌注损伤 ,使心脏收缩及舒张功能明显高于缺血再灌注组 ,MDA生成下降 ,SOD活性增加 ;加B1650 ,这种保护作用消失。结论 :缓激肽参与缺血预处理心肌保护的作用是通过激活缓激肽B2 受体介导的     

Remote ischaemic preconditioning modifies serum apolipoprotein D,met‐enkephalin,adenosine, and nitric oxide in healthy young adults

Remote ischaemic preconditioning (RIPC) has been employed as a non‐invasive protective intervention against myocardial ischaemia–reperfusion injury in animal studies. However, the underlying mechanisms are incompletely defined in humans and its clinical efficacy has been inconclusive. As advanced age, disease, and drugs may confound RIPC mechanisms in patients, our aim is to measure whether RIPC evokes release of adenosine, bradykinin, met‐enkephalin, nitric oxide, and apolipoproteins in healthy young adults. Healthy subjects (n = 18, 9 males, 23 ± 1.5 years old; 9 females, 23 ± 1.8 years old) participated after informed consent. RIPC was applied using a blood pressure cuff to the dominant arms for four cycles of 5‐minute cuff inflation (ischaemia) and 5‐minute cuff deflation (reperfusion). Blood was sampled at baseline and immediately after the final cuff deflation (Post‐RIPC). Baseline and Post‐RIPC plasma levels of adenosine, bradykinin, met‐enkephalin, apolipoprotein A‐1 (ApoA‐1), apolipoprotein D (ApoD), and nitric oxide (as nitrite) were measured via ELISA and high‐performance liquid chromatography. Mean (±SD) baseline levels of adenosine, bradykinin, met‐enkephalin, ApoA‐1, ApoD, and nitrite in healthy young adults were 13.8 ± 6.5 ng/mL, 2.6 ± 1.9 μg/mL, 594.1 ± 197.4 pg/mL, 3.0 ± 0.7 mg/mL, 22.2 ± 4.0 μg/mL, and 49.8 ± 13.4 nmol/L, respectively. Post‐RIPC adenosine and nitrite levels increased (59.5 ± 37.9%, P < .0001; 32.2 ± 19.5%, P < .0001), whereas met‐enkephalin and ApoD levels marginally decreased (5.3 ± 14.0%, P = .04; 10.8 ± 20.5%, P = .04). Post‐RIPC levels were not influenced by sex, age, blood pressure, waist circumference, or BMI. RIPC produces increased levels of adenosine and nitrites, and decreased met‐enkephalin and ApoD in the plasma of young healthy adults.