The Effect of Verapamil on Response of Coronary Vasomotion to Handgrip Exercise in Symptomatic Patients with Hypertrophic Cardiomyopathy

Objectives. To assess the effect of verapamil on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to handgrip exercise in symptomatic HCM patients. Design. In 13 patients with HCM, the CBFV was detected in the distal portion of left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. The peak diastolic CBFV and coronary vascular resistance index (calculated as the ratio of mean aortic pressure to CBFV) was measured at baseline and during handgrip exercise. Changes of these parameters induced by the exercise (expressed as the percentage of baseline values) were compared on verapamil treatment and after verapamil withdrawal. The same measurements were obtained in 10 healthy control subject. Results. In HCM patients, the increase in CBFV during exercise was significantly higher on than off verapamil therapy (16.2 ± 5% versus 6.8 ± 3.8%, p < 0.001). In healthy controls, exercise-induced increase in CBFV was comparable to CBFV changes in HCM patients receiving verapamil (17.4 ± 5.7 versus 16.2 ± 5%, p < 0.05) and was significantly greater than the CBFV response in HCM patients off verapamil (17.4 ± 5.7% versus 6.8 ± 3.8 % p < 0.005). During exercise the coronary vascular resistance index decreased on verapamil and increased after drug withdrawal (–5.8 ± 5.6% versus 1.1 ± 5.1%, p < 0.001). In healthy controls the coronary vascular resistance index decreased during exercise –8.5 ± 4.5% to similar extent as in HCM patients on verapamil. Conclusion. In HCM symptomatic patients, verapamil improved coronary vasomotor response to physical stress. Verapamil was able to restore adequate vasodilator response to handgrip exercise.     

Fogarty导管在动静脉内瘘中的应用

目的通过使用Fogarty导管扩张血管的方法,提高血液透析动静脉内瘘术中血管条件不良时的通畅率。方法总结分析12例血管纤细、狭窄,经Fogarty导管扩张后行动静脉内瘘术患者的临床资料。结果12例患者10例血管通路通畅,无血栓形成;2例3 d后血管通路血栓形成,再次行取栓扩张重新吻合后血管通路通畅。结论慢性肾病患者需要建立动静脉内瘘完成维持生命的血液透析,在血管条件不理想,纤细、狭窄时使用Fogarty导管扩张血管,仔细修剪吻合口,能够建立良好的血管通路。     

The effect of glibenclamide on acetylcholine and sodium nitroprusside induced vasodilatation in human cutaneous microcirculation

Objective: K_ATP channels have an important regulatory role in resting vascular tone and during hypoxia. Their role in endothelium dependent and independent vasodilatation in human skin microcirculation is less known. Methods: We monitored the laser‐Doppler (LD) response in 14 healthy male volunteers on the skin of the forearm. In the case of endothelium dependent vasodilatation [acetylcholine (ACh) induced], a saline solution (used as control) or a solution of glibenclamide (K_ATP channel blocker) were randomly injected each into a distinct measurement site on different forearms followed by the iontophoresis of ACh. In the case of endothelium dependent vasodilatation with the inhibition of prostaglandin production, diclofenac (cyclooxygenase inhibitor) or the combination of diclofenac and glibenclamide were randomly injected each into a distinct measurement site on different forearms followed by the iontophoresis of ACh. In the case of endothelium independent vasodilatation [sodium nitroprusside (SNP) induced], a saline solution or glibenclamide were randomly injected each into a distinct measurement site on different forearms, iontophoresis of SNP followed. Results: Glibenclamide alone, diclofenac alone or the combination of glibenclamide and diclofenac reduced the LD flux values during rest and after ACh application (P<0·05). The reduction of LD flux in ACh mediated vasodilatation was greatest when using the combination of glibenclamide and diclofenac. In the case of SNP application, there was also a significantly lower LD flux rise for glibenclamide in comparison with the saline solution (P<0·05). Conclusions: K_ATP channels play an important role in human cutaneous vasodilatation induced by ACh and SNP.     

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

Aims: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using¹⁸fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day,n=16) for 12weeks.¹⁸F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%).¹⁸F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of¹⁸F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.     

蛋白激酶C不同亚型对丙泊酚血管舒张作用的影响

目的探讨丙泊酚的血管舒张作用与蛋白激酶C(PKC)不同亚型间的关系。方法将SD大鼠胸主动脉环随机分为内皮完整组(n=36)和去内皮组(n=36),每组各分6个亚组:①10 nmol/L Go6976+1×10-6mol/L去甲肾上腺素(NA)+丙泊酚处理组(n=6);②10μmol/L Rottlerin+1×10-6mol/L NA+丙泊酚处理组(n=6);③2μmol/L PKCε-Pseudo(假底物)+1×10-6mol/L NA+丙泊酚处理组(n=6);④2μmol/L PKCθ-Pseudo+1×10-6mol/L NA+丙泊酚处理组(n=6);⑤2μmol/L PKCζ-Pseudo+1×10-6mol/L NA+丙泊酚处理组(n=6);⑥1×10-6mol/L NA+丙泊酚处理组(对照组,n=6)。PKCα抑制剂Go6976,PKCδ抑制剂Rottlerin,PKCζ、θ和ε假底物孵育血管环30 min后,加1×10-6mol/L NA收缩血管环达峰值,每15 min加递增浓度的丙泊酚(1×10-6、5×10-6、1×10-5、5×10-5、1×10-4mol/L),观察血管张力的变化。结果内...     

茉莉花水提物对大鼠胸主动脉的舒张作用及机制

 目的 观察中药茉莉花水提物（AEJ）的血管舒张效应并探讨其机制。方法 采用大鼠胸主动脉环灌流,记录张力的变化;激光扫描共聚焦显微镜技术检测血管平滑肌细胞内 Ca2+浓度。结果 AEJ（0.375～6 g·L-1）能够浓度依赖性降低苯肾上腺素（PE,10 μmol·L-1)及 KCl (60 mmol·L-1)引起的主动脉环张力。在无钙环境下,AEJ 能抑制高浓度氯化钾 (KCl 60 mmol·L-1)环境下累计加入 CaCl₂(0.5～8 mmol·L-1)引起的收缩,抑制 PE (10 μmol·L-1) 引起的去内皮主动脉环的短暂收缩 (P<0.01)。钾通道阻断剂 4-氨基吡啶(5 mmol·L-1)可显著抑制 AEJ 的舒血管作用。激光扫描共聚焦检测细胞内 Ca2+的结果表明,AEJ 浓度依赖性（6,12 g·L-1）降低了 KCl 除极诱导的滑肌细胞胞浆内 Ca2+的升高幅度（P<0.05）。结论 AEJ 能够浓度依赖性舒张大鼠胸主动脉,其作用机制可能是减少 Ca2+经电压依赖性钙通道和受体操纵性钙通道流入血管平滑肌细胞及抑制内质网内 Ca2+释放有关;电压敏感型 K+通道（K_V）的激活部分参与了 AEJ 舒血管作用。     

cAMP-PKA信号转导在SO2衍生物舒张血管中作用

目的 研究环腺苷酸单磷酸-蛋白激酶A(cAMP-PKA)信号转导系统在SO₂衍生物舒张血管中的作用.方法 当SO₂衍生物诱发该血管环舒张时,采用放射免疫法检测血管环组织环腺苷酸单磷酸(cAMP)、环鸟苷酸单磷酸(cGMP)、前列环素(PGI₂)和血栓素(TXA2)的稳定代谢产物6-酮-前列腺素F1a(6-keto-PGF1a,6-keto)和血栓素B2(TXB₂)的含量,并用32P掺入底物法测定组织中的蛋白激酶A(PKA)活性.结果 SO₂衍生物可引起血管组织中cAMP、6-kceto(即PGI₂)含量及PKA活性增加,其增加程度与内皮无关;SO₂衍生物不能引起血管环cGMP和TXB₂含量的变化,但可引起cAMP/cGMP和6-keto/TXB₂比值显著升高.结论 SO₂衍生物可使PGI₂-cAMP-PKA信号通路活化,这可能是SO₂导致血管舒张的机制之一.     

Endothelium-dependent relaxation to hydrogen peroxide in canine basilar artery: a potential new cerebral dilator mechanism

In prostglandin F_2α(PGF_2α)-precontracted isolated canine basilar arterial rings, hydrogen peroxide (H₂O₂) produced endothelium-dependent relaxations at concentrations of from 4.4 × 10⁻⁷–∼4.4 × 10⁻⁵ M. Removal of extracellular Ca²⁺ ([Ca²⁺]₀) attenuated the relaxant effects of H₂O₂. Complete inhibition of H₂O₂ relaxant action was obtained after buffering intracellular Ca²⁺ ([Ca²⁺]_i), in the endothelial cells, with 10 μM 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM). The H₂O₂-induced relaxations could be abolished completely by 1200 u/ml catalase and was suppressed significantly by 0.5 μM atropine, 150 μM N^G-monomethyl-arginine (L-NMMA), 50 μM N^G-nitro-L-arginine methyl ester (L-NAME), 1 μM Fe²⁺, or 5 μM methylene blue. These inhibitory effects of L-NMMA, L-NAME, or atropine could be reversed partly by 50 μM L-arginine. The Fe²⁺ inhibition of H₂O₂-stimulated relaxation was reduced significantly by either 1 mM deferoxamine (a Fe²⁺ chelator) or 100 μM dimethyl sulfoxide (DMSO, a ^•OH scavenger). Such relaxant effects of H₂O₂ were enhanced, significantly, by an acetylcholinesterase antagonist, neostigmine. A variety of pharmacological antagonists (of diverse vasodilator agents) could not inhibit the relaxant action of H₂O₂. Our observations suggest that at suitable pathophysiological concentrations, H₂O₂ could induce release of an endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO), from endothelial cells of the canine cerebral artery. The H₂O₂ relaxant effects are clearly Ca²⁺-dependent, require formation of cyclic guanosine monophosphate (cGMP), and may be associated with release of endogenous acetylcholine (ACh).     

Diabetic ketosis activates lymphomonocyte-inducible nitric oxide synthase.

AIMS: Inappropriate production of nitric oxide (NO) may be responsible for the haemodynamic disturbances of diabetic ketoacidosis. We investigated whether this metabolic condition is associated with increased plasma nitrate (the stable oxidation product of NO) levels and NO synthase gene expression in lymphomonocytes. RESEARCH DESIGN AND METHODS: Plasma nitrate concentrations, lymphomonocyte-inducible nitric oxide synthase (iNOS) gene expression, tumour necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin were measured in 11 Type 1 diabetic patients at baseline, during mild ketosis and after euglycaemia was re-established. RESULTS: During diabetic ketosis plasma nitrate concentrations were higher (18 (16-21) vs. 9 (7-11) micro mol/l; (95% lower-upper confidence interval) P < 0.05) than at baseline. At baseline lymphomonocyte iNOS mRNA expression and iNOS protein levels were undetectable, but in ketosis both were increased (both at P < 0.0001). After recovery from ketosis, NO3 concentration, iNOS mRNA, and iNOS expression (270 +/- 36%, mean +/- sd) decreased but not significantly. No significant changes were observed in either TNF-alpha or soluble thrombomodulin levels between the three conditions. CONCLUSIONS: Diabetic ketosis is associated with increased nitrate levels and the activation of iNOS expression in circulating lymphomonocytes, but it does not affect either the proinflammatory cytokine TNF-alpha or a marker of endothelial dysfunction such as thrombomodulin. Our data support the hypothesis that, during diabetic ketosis, alterations in NO homeostasis are present in circulating lymphomonocytes.     

EFFECTS OF ENDOTHELIUM-DERIVED RELAXING FACTOR ON THE SMOOTH MUSCLE OF THE RAT TAIL ARTERY

Simultaneous measurements of smooth muscle membrane potential and tension were made from isolated pieces of rat tail artery. A single electrical stimulus to the perivascular nerves produced a transient contraction of the smooth muscle. The amplitude of the contraction was increased after removal of the endothelium. The excitatory junction potentials and action potentials in the smooth muscle had the same amplitudes before and after removal of the endothelium. Tension obtained by direct stimulation of the arterial muscle in guanethidine-treated arteries was also increased by removal of the endothelium. When the artery was constricted by noradrenaline or 5-hydroxytryptamine, electrical stimulation caused a relaxation that was reduced by removing the endothelium. It was concluded that the electrical stimulus released the endothelium-derived relaxing factor (EDRF) which reduced the amount of contractile force that could be produced by an action potential in the smooth muscle.