白藜芦醇对脓毒症血管舒张功能的保护作用及机制

目的探讨白藜芦醇(Res)对脓毒症血管舒张反应性的保护作用及与eNOS和iNOS的关系。方法采用盲肠结扎穿孔复制脓毒症模型,将32只SD大鼠随机分为4组:正常对照组、脓毒症组、常规治疗组(乳酸林格液体复苏+血管活性药多巴胺+头孢呋辛钠)、Res治疗组(Res+常规治疗),每组8只。Res治疗组在模型后尾静脉给予白藜芦醇,12 h后行常规复苏并二次给药,观察4组大鼠肠系膜上动脉(SMA)的舒张反应性、肠系膜微血管动静脉流速、血流动力学、肝肾血流量、肠系膜上动脉eNOS和iNOS的表达及存活率和存活时间的变化。结果与正常对照组相比,脓毒症组大鼠血管舒张反应性明显降低;常规复苏可轻微改善脓毒症大鼠血管舒张反应性;Res可以明显改善脓毒症大鼠肠系膜血管舒张反应性,进一步研究发现,Res通过保护脓毒症大鼠的血管舒张反应性来改善血流动力学和组织器官的灌注量,提高了脓毒症大鼠的存活率和存活时间,机制研究发现Res对脓毒症大鼠血管舒张反应性的保护作用与血管eNOS和iNOS有关。结论白藜芦醇通过改善脓毒症大鼠的血管舒张反应性,从而实现了对整体器官的保护作用。     

阿托伐他汀降脂治疗对血管内皮舒张功能的康复作用

目的探讨阿托伐他汀的降脂作用和对血管内皮依赖性舒张功能的影响。方法42例高胆固醇血症患者应用阿托伐他汀治疗8周,观察治疗前后血清胆固醇变化;40例健康者作对照组。采用高分辨超声技术在治疗前后进行血管内皮依赖性舒张功能检测。结果42例高胆固醇血症患者治疗前肱动脉血流介导性舒张为(3.66±0.72)%,较对照组的(13.18±1.23)%显著减弱(P<0.001);服用阿托伐他汀10~20mg/d8周后,肱动脉内皮舒张功能较治疗前显著改善,为(10.98±1.57)%(P<0.001),且血清胆固醇从(7.11±0.70)mmol/L降至(5.86±0.59)mmol/L(P<0.01)。结论高胆固醇血症患者存在血管内皮依赖性舒张功能障碍,阿托伐他汀不但有明显的降脂作用,而且对血管内皮舒张功能有明显的康复作用。     

单剂量二甲双胍改善急性糖负荷对高血压患者血管内皮功能的损伤

目的探讨单剂量二甲双胍(MF)对原发性高血压患者在急性糖负荷后的内皮依赖性血管舒张功能、血清抗氧化物质及游离脂肪酸的影响。方法入选未经降压治疗的原发性高血压(EH)患者39例,随机分为高血压对照组(EH 组,未服用降压药,n=26)和二甲双胍组(MF 组,服用单剂量 MF,0.5 g/d,n=13);另选择同期健康体检者设为正常对照组(n=15)。入选者禁食12 h 后,口服葡萄糖耐量试验(OGTT)。以高分辨率血管彩超测定糖负荷0、1、2、3 h 后肱动脉血流介导的内皮依赖性血管舒张功能(FMD)。检测血清中超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)、抗超氧阴离子自由基(AntiO_2~-)和游离脂肪酸(FFA)的水平。结果急性糖负荷1 h 后,EH 组和正常对照组的 FMD 显著下降[EH 组(9.5±3.3)%比负荷前(13.6±5.0)%,P<0.05;正常对照组(14.4±5.9)%比负荷前(17.4±5.7)%,P<0.05],MF 抑制糖负荷对 FMD 的影响[MF 组1 h:(14.5±6.2)%比负荷前:(14.5±6.0)%,P>0.05]。急性糖负荷后1 h,EH 组的 SOD...     

An international matched cohort study of the contribution of metabolic impairments to subclinical atherosclerosis in United Kingdom and Jamaican African-Caribbeans

Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucleotide polymorphisms (SNPs), R46L and E670G, in 5783 elderly participants in Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), of whom 43% had a history of vascular disease at baseline, and who were randomized to pravastatin or placebo with followup. In this population 3.5% were carriers of the T allele at R46L, and these subjects had significantly (p < 0.001) lower levels of LDL C (mean, −10%), no difference in LDL C lowering response to pravastatin, and a non-significant 19% unadjusted and 9% adjusted decreased risk of vascular disease at baseline, with no on trial effect. Moreover, 6.0% were carriers of the G allele at E670G with no significant relationships with baseline LDL C, response to pravastatin, or vascular disease risk being observed. Our data support the concept that the rare allele of the R46L SNP at the PCSK9 locus significantly lowers LDL C, but does not greatly reduce CHD risk in an elderly population with a high prevalence of cardiovascular disease.     

Impact of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism: A narrative review

AimsPrimary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English.Data synthesisIn the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting.ConclusionsPTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.     

The cholinomimetic agent carbachol induces headache in healthy subjects

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 µg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (V_MCA) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P  = 0.042) and in the postinfusion period (30–90 min) ( P  = 0.027). Carbachol infusion caused a drop in V_MCA ( P  = 0.003) and an increase in STA diameter ( P  = 0.006), but no increase in the RA diameter ( P  = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.     

Four-week administration of nimesulide, a cyclooxygenase-2 inhibitor, improves endothelial dysfunction in the hindlimb vasculature of streptozotocin-induced diabetic rats

The aim of this study was to examine the effect of chronic administration of nimesulide, a cyclooxygenase-2 inhibitor, on endothelial dysfunction in streptozotocin-induced diabetic rats. Three groups of Sprague-Dawley rats (300–350 g, n = 6) were used. The first group served as normoglycemic control and the second and third groups were rendered diabetic by an intraperitoneal injection of streptozotocin (60 mg/kg). The third group received the selective COX-2 inhibitor, nimesulide (20 mg/kg/day), orally by gavage for 4 weeks while the second group received only drinking water and served as diabetic control. At the end of the treatment period, the rats were anesthetized with urethane (1.2 g/kg) and mean arterial pressure, heart rate and hindlimb blood flow were monitored. This was followed by the injection of acetylcholine (endothelium-dependent vasodilator, 0.1–0.8 μg/kg) and sodium nitroprusside (endothelium-independent vasodilator 1–4 μg/kg). Mean arterial pressure was significantly reduced and hindlimb vascular conductance was not significantly affected in the control diabetic group when compared to the normoglycemic control group. Nimesulide treatment did not cause any significant change in any of the measured hemodynamic parameters. Acetylcholine and sodium nitroprusside induced dose-dependent increases in hindlimb vascular conductance in control normoglycemic rats which were attenuated in diabetic control rats. Nimesulide reversed the attenuation of acetylcholine-induced increase in hindlimb vascular conductance. In conclusion, chronic administration of the selective COX-2 inhibitor, nimesulide improved endothelial dysfunction in the hindlimb vasculature of streptozotocin induced diabetic rats. This suggests that COX-2 products might be involved in the pathogenesis of endothelial dysfunction in streptozotocin-induced diabetic rats.     

Impaired vascular endothelium-dependent relaxation in Henoch-Schönlein purpura

Few reports have focused on vascular endothelial function in children with Henoch-Schönlein purpura (HSP). The purpose of the present study was to assess endothelial function and to follow serial changes from the acute to convalescent phases in children with HSP. Forearm flow-mediated vasodilation was evaluated in 21 patients with HSP, aged 4.0–10.3 years (median 6.2 years), and in 14 control subjects. Vascular dimension, mean velocity, and flow volume were measured by ultrasonography in brachial artery before and after hyperemia, and during incremental infusions of nitroglycerin (0.5, 1.0 g/kg per min). In the controls, significant increases in dimension, mean velocity, and flow volume were observed in reactive hyperemia (P<0.01). In contrast, patients in the acute phase of HSP showed a flow velocity profile indicating a highly resistant forearm circulation, and significantly attenuated responses after hyperemia (P<0.01 vs. control), whereas the responses to nitroglycerin were well preserved. In addition, the impaired hyperemic responses recovered in the convalescent phase, with no significant differences compared with controls. These results clearly suggest that forearm vascular endothelium-dependent relaxation was attenuated in patients with acute HSP.     

Effect of magnesium on mechanical properties of pressurized mesenteric small arteries from old and adult rats

The purpose of the present study was to determine the effects of magnesium (Mg) on the mechanical properties of resistance arteries in adult and old rats. Studies were performed in adult (17 weeks) and old (104 weeks) male Wistar rats. The vasodilatory response and the passive mechanical properties of the wall of isolated perfused and pressurized arterial segments of mesenteric small arteries were investigated after Mg and verapamil application, both known for their calcium antagonistic properties. Mesenteric resistance arteries from old rats exhibited an outward hypertrophic remodelling, with enlargment of the lumen, thickening of the media and enlarged media cross-sectional area. The vasodilatory response induced by the application of increasing extracellular concentrations of Mg and verapamil was significantly smaller in preconstricted mesenteric arteries of old rats than in those of adult rats. Incremental distensibility in response to increasing intravascular pressures did not change. However, the stress-strain curve was shifted to the left in pressurized mesenteric arteries from old rats, indicating arterial wall stiffness. Verapamil (3 micro mol/L) did not modify the stress-strain curves in either adult or aged rats. However, Mg (4.8 mmol/L) significantly shifted the curve to the right in mesenteric arteries from adult rats and, to a greater degree, in those from old rats. Although Mg-induced vasodilatation is impaired in aged rats, increased Mg concentration improved the mechanics of pressurized mesenteric resistance arteries. The fact that Mg decreases arterial stiffness in arteries from old rats suggests that Mg has a beneficial effect on age-related changes to the vascular wall.