Action of ryanodine on neurogenic responses in rat isolated mesenteric small arteries

1. Rat mesenteric arteries (∼250 μm) were set up in a single-channel isometric myograph designed to allow fluorescence measurements concurrent with field stimulation of intramural nerves. Vessels were loaded with 6 μM fura-2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca²⁺]_i were obtained. In other experiments, arteries were loaded with 1 μCi ml⁻¹ [³H]-noradrenaline (NA) for 30 min in order to measure release of [³H]-NA in response to field stimulation to examine whether ryanodine directly inhibited neuronal release of NA.
2. Arteries were activated by single intermittent field stimulation or continuously to excite intrinsic sympathetic nerves, or by cumulative addition of noradrenaline (1 nM–10 μM) to the bathing solution.
3. Pre-incubation with ryanodine markedly inhibited the contraction and [Ca²⁺]_i release in response to single-pulse nerve stimulation. Ryanodine also inhibited an early phasic component of the response to continuous field stimulation and reduced the rate of rise in force in response to continuous field stimulation. However, stable maximal contraction and [Ca²⁺]_i in response to continuous field stimulation as well as maximal responses to exogenous NA were unaffected. Release of [³H]-NA in response to single intermittent field stimulation was not affected by ryanodine when compared to vehicle.
4. Our results suggest that brief intermittent activation of intramural sympathetic nerves increases [Ca²⁺]_i and contracts small arteries primarily by releasing Ca²⁺ from a ryanodine-sensitive intracellular store. In contrast, the stable rise in tone and [Ca²⁺]_i resulting from continuous nerve stimulation may largely depend on sources of Ca²⁺ other than the ryanodine-sensitive intracellular store.

     

Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries

1. This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120–200 μm in diameter, incubated with a selective agonist and the novel ‘antisense'' peptide to part of the human endothelin_A receptor.
2. Groups of vessels (n=6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC₅₀ of 8.16±0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum).
3. Preincubation of six vessels with the antisense peptide ETR p₁/f1 at 1 μM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 μM ETR p₁/f1, there was a significant shift of the concentration-response curve and a lower pEC₅₀ at 7.78±0.09 M (P<0.05). At the highest concentrations of ETR p₁/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 μM, only reached some 10% of the maximal achievable contraction.
4. Increasing ET-1 concentrations up to 2 μM in vessels incubated with 40 μM ETR-p₁/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P<0.001) by approximately one log unit with a pEC₅₀ of 7.13±0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors.
5. At the highest concentrations tested, 40 μM, ETR-p₁/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions.
6. Together, these data suggest that at the rat renal arcuate artery the endothelin_A receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel type of ‘antisense'' peptide in blocking receptor activation.

     

The basal and stimulated release of the endothelium-derived relaxing factor from isolated pig coronary arteries does not interfere with the vascular release of superoxide

Oxygen-derived free radicals, in particular superoxide anions, are known to inactivate the endogenous vasodilator endothelium-derived relaxing factor (EDRF) which is probably identical with the gaseous radical nitric oxide. It is possible that EDRF is not the target of superoxide anions but may also be an endogenous scavenger of this radical.Superoxide anions generated by the vessel wall were measured by a modified lucigenin-enhanced chemiluminescence technique in isolated pig coronary artery rings with intact endothelium.The addition of bovine superoxide dismutase, a scavenger of superoxide anions, decreased the chemiluminescence signal by 40 ± 26% (mean ± SD; P < 0.05; n = 21) indicating reduced generation/release of superoxide anions. In contrast, pretreatment of coronary artery rings with diethyldithiocarbamate, an inhibitor of the intrinsic copper-zinc superoxide dismutase, increased the chemiluminescence response by 136 ± 128°10 (P < 0.05; n = 21). This increase in the chemiluminescence response induced by diethyldithiocarbamate-pretreatment was almost abolished in the presence of added bovine superoxide dismutase. Specific inhibition of the EDRF release with nitro-l-arginine (100 M) did not affect the chemiluminescence response. On the other hand, stimulation of the EDRF release by substance P (10 nM) or addition of the endothelium-mediated relaxant bradykinin (0.1 M) did not affect the chemiluminescence response. Stimulation of the EDRF release with serotonin (0.1 M) significantly reduced the photon emission by 15 ± 16% (n = 27). However, this effect of serotonin on the chemiluminescence response could not be prevented by specific inhibition of the EDRF release with nitro-l-arginine (100 M) but could be prevented by buffering the acidic serotonin solution with NaOH to pH 7.4.Our results suggest that basal and agonist-stimulated release of EDRF in isolated pig coronary artery rings does not interfere with the basal generation/release of superoxide anions derived from the vascular wall. Correspondence to: A. Mugge at the above address     

Syndrome X in women is associated with oestrogen deficiency

This study was undertaken to ascertain whether gynaecologicalhistory or a reduction in ovarian hormones are triggers of anginain menopausal women with a positive exercise test and normalcoronary arteries. The majority of patients with angina pectoris,a positive exercise test and normal coronary arteries are female,suggesting that the female gender may be important in the aetiology.We studied the gynaecological features of 107 women (age 53±9 years) with syndrome X, taken from a population of134 patients including 27 males. Cardiological investigationswere undertaken and detailed gynaecological history obtainedfrom all the female patients. Menopausal status was confirmedby plasma levels of oestradiol-17ß100 pmol. l^–1. In 95 of the 107 female patients, chest pain began either duringthe perimenopausal period (32) or after the menopause (63).Of the 63 menopausal patients, 43 had undergone hysterectomyat an average of 8 ± 6 years prior to the onset of chestpain. The incidence of hysterectomy in the study population(40%) was four times greater than that of an age-matched population.These findings confirm that the majority of patients with syndromeX are women in whom the chest pain began after the onset ofmenopause. Ovarian hormone deficiency may, therefore, play arole in the onset of syndrome X in female patients.     

Intramural hydatid cysts of pulmonary arteries: CT and MR findings

Involvement of the pulmonary artery by echinococcosis usually occurs due to pulmonary embolization after rupture of the cyst in the right ventricle or, rarely, by dissemenation from a hepatic focus. This paper presents an adult patient with intramural hydatid cysts of the pulmonary arteries, which apparently grew slowly toward the lumina resulting in complete luminal occlusion, enabling sufficient time for development of sufficient perfusion from the bronchial arteries. The condition apparently resulted from embryos of the parasite, which entered the vasa vasorum of the pulmonary arteries, a previously unreported mechanism.     

原代培养人脐动脉内皮细胞的超微结构

对不用贴附基质和生长因子情况下原代培养７２ｈ的人脐动脉内皮细胞（ＨＵＡＥＣ）进行了透射电镜观察。电镜下ＨＵＡＥＣ形态不规则,细胞器丰富。核周有散在的滑面内质网、粗面内质网及较多的线粒体,后者有些为板层状嵴,另一些为管泡状嵴。细胞膜下可见微管,胞质内有大量循同一方向排列的微丝。Ｗｅｉｂｅｌ Ｐａｌａｄｅ小体内含涡旋状排列的细管。胞质内含丰富的糖原颗粒。细胞核内常染色质较多,异染色质主要分布于核膜下。有时可见处于无丝分裂状态的细胞,核已分裂为二,但二者间仍有核膜相连。内皮细胞间以紧密连接或中间连接的方式相连。以上结果表明：人脐动脉内皮细胞在体外培养条件下代谢功能旺盛,且具有参与脂类代谢的细胞器,细胞以无丝分裂方式增殖。     

肺血管磁共振成像:比较二维TOF、三维TOF及Gd-DTPA增强

目的 探讨２种常用的ＭＲ血管成像方法对正常肺动脉图像质量的影响及Ｇｄ－ＤＴＰＡ知其中的作用。材料和方法：用１．０Ｔｅｓｌａ超导ＴＲＩ系统,体线圈技术,随机选择无人心肺疾患志愿者４６例,行２Ｄ ｔｕｒｂｏ ＦＬＡＳＨ和／或３Ｄ ＦＩＳＰ肺部ＭＲＡ检查共１１３次,行Ｇｄ－ＤＴＰＡ增强后２Ｄ ｔｕｒｂｌ ＦＬＡＳＨ和／或３Ｄ ＦＩＳＰ扫描共４７次。计算机测量肺动脉和背景噪声的信号强度,计算出肺动脉的信噪     

Temporary strecker stent for management of acute dissection in popliteal and crural arteries

Stent placement is a widely used bail-out treatment for dissection of peripheral arteries. Below the level of the superficial femoral artery permanent stenting is complicated by a high incidence of subacute thrombosis and restenosis. We present two cases of arterial occlusion due to acute iatrogenic dissection of the popliteal and distal fibular arteries. Successful treatment was achieved with a new bail-out procedure. Strecker stents were implanted to seal off the dissection flap. Stents were retrieved easily after 24 hr using a myocardial biopsy forceps. After stent retrieval the temporarily stented segments were patent and showed a larger lumen compared with segments treated by balloon dilatation alone. Temporary stenting is a simple and safe procedure and offers the advantage of tacking up dissection membranes and preventing recoil. Persistent presence of a metallic implant as a source of continued injury and stimulus for intimal proliferation is avoided.     

Effects of propofol on isolated human pial arteries

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.     

Pulmonary magnetic resonance angiography

In the past few years magnetic resonance angiography (MRA) of the pulmonary vasculature has advanced from a research tool to a clinically relevant imaging modality. Early 2D phase-contrast and time-of-flight (TOF) sequences without the use of contrast agents were time-consuming and limited by considerable imaging and motion artifacts. Since the introduction of MR scanners with stronger gradients (> 20 mT/m) and contrast-enhanced techniques, imaging of the pulmonary vasculature with adequate spatial resolution within a single breathhold is now possible. In the detection of pulmonary embolism in the lobar or segmental arteries, contrast-enhanced MRA is now on the verge of being considered an established modality, possibly competing with conventional pulmonary angiography and contrast-enhanced helical CT. In the future, utilization of phased-array torso coils, the application of navigator pulse sequences, and 3D time-resolved ultrafast MRA will overcome the final limitations of current techniques. Blood-pool MR contrast agents may provide a “one-stop-shopping” approach to the investigation of lower extremity veins and pulmonary arteries in venous thromboembolism.