妊高征血管功能改变及其超声学检测的相关研究进展

妊娠高血压综合征是导致孕产妇和围产期妇女发病、死亡的主要原因之一。研究表明,胎盘滋养层细胞功能障碍及母体血管系统内皮功能障碍是妊高征始发的病理生理学中心环节。本文对高频超声检查对妊高征潜在的预测价值进行综述。     

Improved results of vascular reconstruction in pediatric and young adult patients with renovascular hypertension

From 1955 to 1988, 56 patients 21 years old or younger underwent surgical treatment for renovascular hypertension at our clinic. The cause of renal artery disease was fibrous dysplasia in 53 patients, Takayasu's arteritis in 2 or an arterial aneurysm in 1. Bilateral or branch renal artery disease, and extrarenal arterial disease were present in 16, 23 and 11 patients, respectively. The results of 28 patients treated from 1955 to 1977 (group 1) were compared to those of 28 patients treated from 1978 to 1988 (group 2). Hypertension was cured or improved postoperatively in 83% of the patients from group 1 and in 96% from group 2 (p = 0.07). However, this outcome was achieved through surgical revascularization in only 48% of the patients from group 1 compared to 96% from group 2 (p = 0.0002). A multivariate analysis revealed that the only significant variable related to clinical outcome was the era of treatment, which reflects the improved technical efficacy of revascularization during the last decade. Aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. It currently is possible to achieve amelioration of hypertension and preservation of renal function in most young patients with renal artery disease.     

Vitamin D and calcium metabolism in hypertension and vascular smooth muscle cell function

Disturbances in extracellular (systemic) and intracellular calcium metabolism have been demonstrated. Intracellular free calcium in vascular smooth muscle cells is elevated, which is believed to be the final determinant of vascular tone, thus blood pressure. This hypothesis is supported by the fact that calcium channel blocker reduces blood pressure in hypertension by blocking both receptor-operated and potential-operated calcium channel. On the other hand, calcium balance appears to be negative in hypertension and dietary supplement of calcium has been demonstrated to be effective in reduction of blood pressure in both animals and humans with high blood pressure. The latter observation seems to be opposite to the effect of calcium channel blocker, since restored calcium balance may increase intracellular free calcium concentration by supplying higher amount of extracellular (plasma) calcium to the cell membmane, which is leaky in hypertension. The effect of dietary calcium supplement may be explained by changes in calcium regulating hormones but not calciumper se. Recent data on calcium metabolism in the spontaneously hypertensive rats and effect of vitamin D in vascular smooth muncle cells will be discussed in relation to the regulation of vascular tone and blood pressure.     

Vitamin D and calcium metabolism in hypertension and vascular smooth muscle cell function

Disturbances in extracellular (systemic) and intracellular calcium metabolism have been demonstrated. Intracellular free calcium in vascular smooth muscle cells is elevated, which is believed to be the final determinant of vascular tone, thus blood pressure. This hypothesis is supported by the fact that calcium channel blocker reduces blood pressure in hypertension by blocking both receptor-operated and potential-operated calcium channel. On the other hand, calcium balance appears to be negative in hypertension and dietary supplement of calcium has been demonstrated to be effective in reduction of blood pressure in both animals and humans with high blood pressure. The latter observation seems to be opposite to the effect of calcium channel blocker, since restored calcium balance may increase intracellular free calcium concentration by supplying higher amount of extracellular (plasma) calcium to the cell membmane, which is leaky in hypertension. The effect of dietary calcium supplement may be explained by changes in calcium regulating hormones but not calciumper se. Recent data on calcium metabolism in the spontaneously hypertensive rats and effect of vitamin D in vascular smooth muncle cells will be discussed in relation to the regulation of vascular tone and blood pressure.     

Pulmonary vascular structure and function in chronic obstructive pulmonary disease.

Cardiac catheterization data from eight patients with severe chronic obstructive lung disease and pulmonary hypertension at rest (greater than 25 mm Hg) were compared with those obtained from 14 patients with mild to moderate disease whose pulmonary artery pressure was within the normal range at rest (mean 15 (SEM 1) mm Hg), but increased with exercise (30 (2) mm Hg). We obtained lung sections from necropsy material from the group with severe disease, and from surgical specimens in the group with mild to moderate disease, and compared the structure of the vasculature in these groups with that obtained from surgical specimens in a non-smoking control group of seven patients. Oxygen administration either at rest or during exercise did not greatly affect the pulmonary arterial pressures. When cardiac index was plotted against pulmonary artery pressure at rest and during exercise and extrapolated to the axis there was no evidence for a critical closing pressure in either group. The vessels in the groups with mild to moderate and severe chronic obstructive lung disease showed intimal thickening (each 19% (SD 0.5%)) by comparison with the non-smoking group (16% (0.5%]. The group with severe disease, in addition, had medial hypertrophy (27% (0.5%) versus 24% (SD 1%) in the non-smoking group). These data are consistent with the idea that the diseased vessels are distorted and rigid. The lack of effect of breathing oxygen on the vascular response at rest and during exercise suggests that hypoxic vasoconstriction has a minimal role in the pulmonary hypertension of chronic obstructive lung disease. The data suggest that the intimal changes could narrow the vessel calibre in those patients with mild to moderate disease, and that the thickened media present in the vessels from patients with severe disease may act in concert with the enlarged intima to produce more severe vascular obstruction.     

Abnormalities of renin-containing cells in human glomerular and vascular renal diseases

The distribution of renin was investigated by immunofluorescence in human kidney biopsy specimens (27 patients with lipoid nephrosis, 39 with Berger disease, 17 with membranous glomerulonephritis, 5 with thrombotic microangiopathy, and 7 with malignant nephroangiosclerosis). A semiquantitative assessment was carried out. Two ratios were found significatively increased in the study groups as compared with the control group: JGA + and JGA ++ which expressed, respectively, the number of fluorescent JGA in relation to the number of glomerular sections and the number of fluorescent JGA with more than six renin-containing cells (RCC) in relation to the number of immunoreactive JGA. Highest values were observed in patients with thrombotic microangiopathy and malignant nephroangiosclerosis (P less than 0.001). The above immunomorphological parameters were correlated with clinical and laboratory data. A positive dependency was found between JGA + and JGA ++ ratios and a low sodium diet, diuretic therapy and serum creatinine. A negative dependency was seen in the albumin and hemoglobin serum levels. No correlation was found with blood pressure values. These observations suggested that decreased plasma volume and impaired renal function could be factors leading to an increased renin production in the kidney.     

Renovascular hypertension in pediatric patients

Fifteen pediatric patients (ages 5-17 years) with renovascular hypertension (RVH) are reported. The diagnosis was made by arteriogram in all patients as the intravenous pyelogram was not helpful in this group. Five patients had a coarctation of the abdominal aorta. Four of these had associated renal artery stenosis. Renal artery stenosis alone was present in 14 patients, unilateral in 8, and bilateral in 6. Three of the former had a contralateral hypoplastic kidney. A nephrectomy was performed in 2 patients, both of whom continue to be hypertensive. Renal revascularization was performed in 13 patients; one of these died of sepsis. Eight are normotensive, 2 are improved (normotensive with diuretics), and 2 remain hypertensive. The follow-up is from 1 to 15 years.     

Arterial stiffness in pediatric hypertension

Non invasive assessment of large arteries structure and function is a valuable tool for early detection of athero/arteriosclerosis and the cardiovascular risk. The vascular injury is mainly represented by increased arterial stiffness (increased pulse wave velocity--PWV), increased peripheral arteries reflectivity (Aix) and the occurrence of significant atheromatosis (increased clMT). Although well described in adult, there are few data in children regarding the impact of uremia on vascular structure and function. This paper is an overview of the main determinants of arterial compliance in children, focusing on recent data describing the repercussions of hypertension and renal failure in this age group. To date, our group has performed the only case control study in children in order to describe the arterial stiffness, the reflective properties of peripheral arteries as well as the carotid intima-media thickness on 18 children under chronic dialysis treatment (hemodialysis and peritoneal dialysis). Comparing with control cases the dialysed children had a significantly higher PWV and Aix, which reinforce that uremia is associated with arterial stiffness even in children. There were no significant differences on IMT and PWV between hemodialysed and peritoneal dialysed children. In contrast with adult patient data, there was no favourable impact of hemodialysis session over PWv and Aix.     

Association between dairy intake,lipids and vascular structure and function in diabetes

AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure and function.METHODS A 12-mo randomised controlled trial was conducted to determine the effect of increased consumption of fruit, vegetables and dairy, compared to usual diet, on measures of vascular structure and function in adults with type 1 and type 2 diabetes(n = 108). Thispaper comprises post-hoc analyses investigating the relationship between dairy intake, serum lipid species and vascular health. Central and peripheral blood pressure, carotid femoral pulse wave velocity, augmentation index, serum lipid species and dietary intake were measured at baseline and 3-mo. Common carotid artery intima media thickness was measured at baseline and 12-mo.RESULTS Serum lipid species [lysophosphatidylcholine(LPC) 14:0, LPC 15:0, LPC 16:1, phosphatidylcholine(PC) 29:0 PC 30:0, PC 31:0 and cholesterol ester(CE) 14:0] were associated with the change in full fat dairy consumption(rho 0.19-0.25; P 0.05). The 3-mo change in some lipids was positively associated with the 3-mo change in central systolic [LPC 14:0(rho 0.30; P = 0.007), PC 30:0(rho 0.28; P = 0.010)] and diastolic blood pressure [LPC 14:0(rho 0.32; P = 0.004), LPC 15:0(rho 0.23; P = 0.04), LPC 16:1(rho 0.23; P = 0.035), PC 29:0(rho 0.28; P = 0.01), PC 30:0(rho 0.36; P = 0.001), PC 31:0(rho 0.30; P = 0.007)] and 12-mo change in common carotid artery intimal medial thickness [CE 14:0(rho 0.22; P = 0.02)]. Pulse wave velocity and augmentation index were unrelated to dairy and lipid species.CONCLUSION An increase in dairy associated lipids appears to be associated with an increase in blood pressure and common carotid intimal medial thickness.     

Abnormalities of lung function in hay fever.

Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies.     

Noniatrogenic pediatric vascular trauma

Twenty-four noniatrogenic pediatric vascular injuries in 20 patients (75% male; mean age, 14 years) were treated during a 3-year period. Of 18 arterial and six venous injuries, 65% were penetrating and 35% were blunt injuries. Eighty percent of all patients had significant associated injuries that required repair. Angiography was performed in 13 of 20 patients, with four performed during surgery. Repair methods were ligation in two of six venous injuries and three of 18 arterial injuries, primary repair in three of six venous injuries and six of 18 arterial injuries, and autogenous saphenous vein graft in seven of 18 arterial injuries. Exploration and debridement, thrombectomy, and nonoperative management were used in one arterial injury each. Fasciotomy was employed in six of 13 arterial injuries in the extremities. There was one operative death, no reoperations, and no early or late amputations. Mean follow-up of 27 months demonstrated normal palpable and Doppler pulses (by noninvasive testing) distal to all arterial repairs. This study supports an aggressive approach to the diagnosis and treatment of noniatrogenic pediatric vascular trauma, emphasizing the liberal use of fasciotomy and meticulous vascular repair for the successful management of these challenging injuries.     

主动脉缩窄矫治术后血管结构与功能的随访研究

目的 探讨主动脉缩窄矫治术后近、中期血管结构与功能改变.方法 选取20例确诊主动脉缩窄(CoA)并行手术矫治的患儿(CoA组),其中单纯性主动脉缩窄6例,复合性主动脉缩窄(合并其他心内畸形)14例;同期20例单纯室间隔缺损(VSD)患儿(VSD组)作对照,均于术前至术后1年监测血压,超声下颈总动脉内中膜厚度(IMT)和肱动脉血流介导的血管舒张功能(FMD).20例健康儿童(健康组)进行1年的随访.结果 术前、术后1个月、术后6个月、术后1年3组均无高血压临床表现.CoA组的颈总动脉IMT[(0.47±0.10) mm,(0.49±0.10) mm、(0.57±0.07) mm、(0.61±0.07)mm]均高于同期的VSD组[(0.41±0.11) mm,(0.43±0.11) mm,(0.51±0.08) mm,(0.55±0.08) mm]与健康组[(0.40±0,09) mm、(0.42±0.11) mm、(0.50±0.08)mm、(0.57±0.08) mm],差异均有统计学意义,P＜0.05.CoA组的肱动脉FMD[(5.46±1.51)％、(5.71±1.88)％、(5.42±1.69)％、(5.27±1.02)％]均明显低于VSD组[(6.69±1.45)％、(6.66±1.21)％、(6.81±1.03)％、(6.43±1.34)％]和健康组[(6.59±1.84)％,(6.84±1.41)％、(6.91±1.31)％、(6.56±1.62)％],差异均有统计学意义,P＜0.05.而上述两个指标在VSD组与健康组之间均差异无统计学意义,P＞0.05.结论 主动脉缩窄矫治术后患儿仍存在血管结构和内皮功能异常,提示手术纠治主动脉缩窄后血管损害持续存在,可能是主动脉缩窄矫治术后患儿心血管疾病发生率高于健康儿童的原因.     

Modulation of vascular function by neuropeptide Y during development of hypertension in spontaneously hypertensive rats

Neuropeptide Y (NPY) is a sympathetic cotransmitter and a platelet-derived factor which causes vasoconstriction, potentiation of norepinephrine (NE) action, and vascular mitogenic effects. Reciprocally, NE markedly enhances the actions of NPY. We studied vasopressor effects of NPY and sources of peptide release during the development of hypertension in spontaneously hypertensive rats (SHR). Conscious SHR (4 and 16 weeks old) had higher resting plasma levels of NE and epinephrine than age-matched Wistar-Kyoto (WKY) rats, but similar NPY immunoreactivity (NPY-ir) levels in platelet-poor plasmas (PPP). In both strains, NPY-ir levels in PPP were higher in 4-week-old than in older rats. However, at all ages (4–24 weeks) SHR had markedly elevated NPY-ir content in platelet-rich-plasmas than WKY rats, although levels declined with age and hypertension. In the superior mesenteric artery. NPY-ir content (per mg) was significantly higher in 4-week-old but lower in 16-week-old SHR than in WKY rats, suggesting greater sympatho-neural NPY stores and release (leading to depletion) during the development of hypertension. Four-week-old SHR also tended to have higher NPY-ir content in the adrenal medullae and coeliac ganglia but a lower content in the kidney than WKY rats; these differences disappeared with age. Pressor responsiveness to -agonists and NPY were similar in both strains at 4 weeks. While unchanged by age in WKY rats, adrenergic and NPY-mediated vasopressor responses became augmented in 16- to 24-week-old SHR (compared with WKY rats); this hyperresponsiveness was not completely abolished by ganglionic blockade and not observed with vasopressin. The development of adrenergic hyperresponsiveness in SHR in the face of higher circulating catecholamines suggests a defect in downregulation of -adrenoceptors. Since we have previously found that NPY can reverse pressor desensitization to NE, we postulate that increased release of platelet and sympatho-neural NPY leads to impaired adrenergic desensitization, whereas adrenergic/NPY interactions tesult in sensitization to NPY in SHR, and thus may contribute to vascular hyperreactivity and hypertrophy.     

Oxidative stress and vascular damage in hypertension

Oxidative stress, a state of excessive reactive oxidative species activity, is associated with vascular disease states such as hypertension. In this review, we discuss the recent advances in the field of reactive oxidative species-mediated vascular damage in hypertension. These include the identification of redox-sensitive tyrosine kinases, the characterization of enzymatic sources of superoxide production in human blood vessels, and their relationship with vascular damage in atherosclerosis and hypertension. Finally, recent developments in the search for strategies to attenuate vascular oxidative stress are reviewed.     

肿瘤坏死因子-α对人脐静脉血管内皮细胞结构和功能的影响

目的 观察人肿瘤坏死因子-α(TNF-α)对人脐静脉血管内皮细胞EA.hy926结构和功能的影响,并探讨其作用机制.方法 培养人脐静脉血管内皮细胞EA.hy926,分组加入1、10、100 μg/L TNF-α培养24 h,或加入100 μg/L TNF-α培养3、8、12、24 h,Western blot检测细胞中血管扩张刺激磷蛋白(VASP)的表达水平;实时定量聚合酶链反应(Real-time PCR)检测细胞中VASPmRNA的表达水平,流式细胞仪检测细胞凋亡,透射电子显微镜观察细胞超微结构的变化.结果 TNF-α干预24h不同浓度组VASP mRNA水平分别为0.993±0.045(对照组)、0.801±0.022(1 μg/L)、0.626 ±0.018(10 μg/L)、0.529±0.017(100 μg/L);蛋白水平分别为0.849±0.021(对照组)、0.788±0.028(1μg/L)、0.364 ±0.018(10 μg/L)、0.317±0.023(100 μg/L);细胞凋亡率分别为(2.5±1.0)％(对照组)、(14.0±1.1)％(1 μg/L)、(24.4±3.8)％(10 μg/L)、(36.0±2.5)％(100 μg/L).100 μg/L TNF-α干预不同时间组VASP mRNA表达分别为0.829 ±0.051(3 h)、0.741±0.029(8 h)、0.669 ±0.026(12 h)、0.528 ±0.017(24 h),蛋白水平分别为0.528±0.201(3 h)、0.470±0.016(8 h)、0.299±0.015(12 h)、0.298±0.016(24 h);细胞凋亡率分别为(5.4±0.9)％(3 h)、(11.4±1.2)％(8 h)、(21.2±1.4)％(12 h)、(36.3±2.1)％(24 h).VASPmRNA及蛋白水平均呈时间及剂量依赖表达降低(P＜0.05),细胞凋亡率呈时间及剂量依赖升高(P＜0.05).结论 TNF-α通过破坏血管内皮细胞结构和功能导致血管内皮细胞通透性增高,呈时间与剂量依赖性.