Reactive oxygen species in vascular biology: implications in hypertension

Reactive oxygen species (ROS), including superoxide (·O₂^–), hydrogen peroxide (H₂O₂), and hydroxyl anion (OH-), and reactive nitrogen species, such as nitric oxide (NO) and peroxynitrite (ONOO^–), are biologically important O₂ derivatives that are increasingly recognized to be important in vascular biology through their oxidation/reduction (redox) potential. All vascular cell types (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) produce ROS, primarily via cell membrane-associated NAD(P)H oxidase. Reactive oxygen species regulate vascular function by modulating cell growth, apoptosis/anoikis, migration, inflammation, secretion, and extracellular matrix protein production. An imbalance in redox state where pro-oxidants overwhelm anti-oxidant capacity results in oxidative stress. Oxidative stress and associated oxidative damage are mediators of vascular injury and inflammation in many cardiovascular diseases, including hypertension, hyperlipidemia, and diabetes. Increased generation of ROS has been demonstrated in experimental and human hypertension. Anti-oxidants and agents that interrupt NAD(P)H oxidase-driven ·O₂^– production regress vascular remodeling, improve endothelial function, reduce inflammation, and decrease blood pressure in hypertensive models. This experimental evidence has evoked considerable interest because of the possibilities that therapies targeted against reactive oxygen intermediates, by decreasing generation of ROS and/or by increasing availability of antioxidants, may be useful in minimizing vascular injury and hypertensive end organ damage. The present chapter focuses on the importance of ROS in vascular biology and discusses the role of oxidative stress in vascular damage in hypertension.     

LncRNA-NEAT1对妊娠期高血压大鼠JAK2/STAT3信号通路、炎症反应和妊娠结局的影响

摘要 目的：探讨LncRNA-NEAT1对妊娠期高血压大鼠JAK2/STAT3信号通路、炎症反应和妊娠结局的影响。方法：采用注射L-精氨酸甲酯的方法构建妊娠期高血压大鼠模型。采用Western blot检测JAK2/STAT3信号通路蛋白表达;采用ELISA法检测炎症因子和血管内皮损伤因子。观察并记录大鼠24 h蛋白尿、尾静脉压和死胎率。结果：与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更高（P＜0.05）;与模型组相比,LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更低（P＜0.05）,而LncRNA-NEAT1过表达组JAK2、STAT3的蛋白表达水平明显更高（P＜0.05）;与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和sICAM-1水平明显更高,而NO水平明显更低（P＜0.05）;与模型组相比,LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和sICAM-1水平明显更高（P＜0.05）,而NO水平明显更低（P＜0.05）,而LncRNA-NEAT1过表达组ET-1和sICAM-1表达水平明显更高,而NO明显更低（P＜0.05）;与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更高（P＜0.05）;与模型组相比,LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更低（P＜0.05）,而LncRNA-NEAT1过表达组TNF-α、IL-1β、IL-18表达水平明显更高（P＜0.05）;与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组尾静脉压和24h蛋白尿水平明显更高（P＜0.05）;与模型组相比,LncRNA-NEAT1抑制组尾静脉压和24 h蛋白尿表达水平明显更低（P＜0.05）,而LncRNA-NEAT1过表达组尾静脉压和24 h蛋白尿表达水平明显更高（P＜0.05）;LncRNA-NEAT1过表达组（21.56%）死胎率显著高于模型组（16.72%）和LncRNA-NEAT1抑制组（5.65%）。结论：妊娠期糖尿病大鼠LncRNA-NEAT1的表达下调可抑制JAK2/STAT3信号通路的表达并下调下游促炎因子的表达,进而缓解血管内皮损伤降低死胎率。     

Effect of diet on serotonergic neurotransmission in depression

Depression is characterized by sadness, purposelessness, irritability, and impaired body functions. Depression causes severe symptoms for several weeks, and dysthymia, which may cause chronic, low-grade symptoms. Treatment of depression involves psychotherapy, medications, or phototherapy. Clinical and experimental evidence indicates that an appropriate diet can reduce symptoms of depression. The neurotransmitter, serotonin (5-HT), synthesized in the brain, plays an important role in mood alleviation, satiety, and sleep regulation. Although certain fruits and vegetables are rich in 5-HT, it is not easily accessible to the CNS due to blood brain barrier. However the serotonin precursor, tryptophan, can readily pass through the blood brain barrier. Tryptophan is converted to 5-HT by tryptophan hydroxylase and 5-HTP decarboxylase, respectively, in the presence of pyridoxal phosphate, derived from vitamin B₆. Hence diets poor in tryptophan may induce depression as this essential amino acid is not naturally abundant even in protein-rich foods. Tryptophan-rich diet is important in patients susceptible to depression such as certain females during pre and postmenstrual phase, post-traumatic stress disorder, chronic pain, cancer, epilepsy, Parkinson’s disease, Alzheimer’s disease, schizophrenia, and drug addiction. Carbohydrate-rich diet triggers insulin response to enhance the bioavailability of tryptophan in the CNS which is responsible for increased craving of carbohydrate diets. Although serotonin reuptake inhibitors (SSRIs) are prescribed to obese patients with depressive symptoms, these agents are incapable of precisely regulating the CNS serotonin and may cause life-threatening adverse effects in the presence of monoamine oxidase inhibitors. However, CNS serotonin synthesis can be controlled by proper intake of tryptophan-rich diet. This report highlights the clinical significance of tryptophan-rich diet and vitamin B₆ to boost serotonergic neurotransmission in depression observed in various neurodegenerative diseases. However pharmacological interventions to modulate serotonergic neurotransmission in depression, remains clinically significant. Depression may involve several other molecular mechanisms as discussed briefly in this report.     

微创颅内血肿清除术对神经细胞损伤因子及血清炎症因子的影响

本研究选取2015年6月至2017年6月我院收治的高血压脑出血患者124例,根据不同的治疗方法分为对照组和观察组。对照组患者采用常规治疗,观察组患者采用常规治疗联合微创颅内血肿清除术治疗,分析微创颅内血肿清除术对脑出血血清铁蛋白(SF)、神经营养因子(NTF)水平以及血清中炎症因子的影响及临床治疗效果。结果表明,治疗前,两组患者出血量、昏迷程度评分比较无统计学差异(p>0.05);治疗后,观察组患者出血量、昏迷程度评分低于对照组(p<0.05)。治疗前,两组患者MMP-9、SF、NTF、GFAP、TNF-α、hs-CRP水平比较无统计学差异(p>0.05);治疗后,观察组患者MMP-9、SF、NTF、GFAP、TNF-α、hs-CRP水平低于对照组(p<0.05)。治疗前,两组患者神经功能评分比较无统计学差异(p>0.05);治疗7 d、14d后,观察组患者神经功能评分低于对照组(p<0.05)。本研究的结果初步说明,微创颅内血肿清除术治疗脑出血可减少患者出血量,降低患者血清炎症因子水平及神经细胞损伤因子的表达水平,改善患者神经功能。     

经颅多普勒超声产科临床应用初探

本文采用经颅多普勒超声(TCD)技术对三组足月初产孕妇共30例进行了TCD主要指标的测定,经统计学处理,正常组、轻度妊高征组的TCD主要指标均在正常人的范围内。而中度、重度妊高征组的TCD主要指标高于正常范围,有显著差异(P<0.0005),左右两侧血管的血流速度不相等,差异超过19.5cm/s。作者等认为TCD技术是一种操作简单,无创伤性、重复,性好、数据可靠的新型检测手段。将TCD作为中度,重度妊高征足月初产孕妇产前、产后的主要监护手段是有一定的现实临床意义。     

肠道菌群与高血压病主要危险因素的相关性及 中药干预研究现状

近年来国内、外文献报道高血压病的发生可能与肠道菌群失调相关。肠道菌群与高血压病主要危险因素(肥胖、高血脂、糖尿病、代谢综合征、动脉粥样硬化)具有一定的相关性,某些益生菌或其发酵产品可能通过改善肠道菌群的方式为高血压病的治疗提供新的思路和途径。近年来研究显示中药具有较长的肠道停留时间,从而有利于其发挥调节肠道菌群的作用,提示某些中药具有调节肠道菌群的作用。但目前国内、外尚无关于中药直接通过肠道菌群作用而干预高血压病的文献报道,而近年来国内有研究显示肠道菌群可能是中药干预高血压病主要危险因素的作用机制之一。     

Analysis of blood lead level and its clinical significance among occupational exposed painters in chennai based population: A cross sectional study

Introduction and aimLead is a ubiquitous element found in the earth crust. There is no known physiologic role of lead in human body and hence any amount of lead present in human tissue considered as a contamination. Several studies on lead toxicity show that, occupational exposure remains the main source for lead toxicity and is emerging as important public health problem. Burden and severity of occupational exposure of lead and its clinical significance are gaining more interest in the field of toxicology. Only limited studies are available and there is scarcity of epidemiology data to assess the blood lead levels of workers and the contribution of common workplace practices to lead exposure in India especially from our region. So, the current study is designed to assess the blood lead levels (BLL) and its clinical significance among high risk workers especially painters working in the construction and public private sector in Chennai based population.Materials and methodsThis cross-sectional case control study included 122 painters and 122 healthy individuals. A detailed questionnaire about demographic details, personal habits, work related safety precautions, presenting symptoms of lead toxicity were given to painter followed by detailed medical examination and blood investigations including blood lead levels were collected and statistically analyzed. The t-test were used to compare mean blood lead levels and to investigate the associations between specific job type, use of self-protection device,sex, service years and occurrence of non-specific symptoms with BLLs.ResultsThe mean BLL of the painters were less than the recommended threshold level. Among painters 13.1% were categorized under BLL > 10 μg/dL. The higher BLL among the painters were directly proportional to year of experience and poor usage of personal protective materials. The levels of Hb, HCT and eosinophil were much correlated with lead toxicity. A marginal significance were observed in some parameters especially urea and creatinine when compared with control. The Cognitive dysfunction, hypertension and renal dysfunction were also observed among the painters.ConclusionThe BLL in painters among our group were minimal compared to biological reference value. Duration of exposure and association of patient’s clinical features like cognitive dysfunction, hypertension and renal dysfunction conditions were observed and this should be carefully monitored and study on huge population of painters with longitudinal aspect is recommended to rule out the clinical correlation of lead toxicity.     

Effects of angiotensin II on the spontaneous activity of rostral ventrolateral medullary cardiovascular neurons and blood pressure in spontaneously hypertensive rats

The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesthetized spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar Kyoto rat (WKY). It was found that Ang II elicited dose-dependent excitatory responses in a subpopulation of RVL cardiovascular neurons, followed by a subsequent increase in blood pressure. These effects of Ang II were significantly greater in SHR than in WKY. The effects were attenuated or abolished by co-administration of Ang II antagonist, [Sar¹, Ile⁸]-Ang II. Pre-administration of [Sar¹, Ile⁸]-Ang II to RVL using bilateral microinjection attenuated the blood pressure effects of intracerebroventricularly administered Ang II by as much as 70%. These results indicated that spinal projecting RVL cardiovascular neurons are important in mediating the pressor action of Ang II. The enhanced sensitivity and responsiveness of RVL cardiovascular neurons to Ang II may be pertinent to the genesis of hypertension in adult SHR.     

Beta-adrenergic mechanisms in arterial hemodynamics: A comparison between normotensive and hypertensive rats

The purpose of this study was to determine whether -adrenergically mediated cardiovascular functions such as arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), peripheral resistance (R_p), arterial impedance (Z_c), mean arterial compliance (C_m) and pulse wave reflection (P_b) were altered in the spontaneously hypertensive rat (SHR) compared to the normotensive Wistar Kyoto rat (WKY). In pentobarbital-anesthetized and artificially ventilated rats, the aortic pressure wave was recorded with a high-fidelity Millar sensor, and aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform so as to analyze impedance spectra. Acute -adrenergic blockade was produced by an intravenous injection of propranolol (nonselective) and atenolol (selective ₁-blocker) at doses of 2 and 5 mg/kg, respectively. Steady-state parameters were obtained 15–20 min after intravenous administration. The SHR had higher AP, HR, R_p and Z_c than the WKY. SV and CO remained unaltered while C_m was lower. In response to propranolol, the mean AP was increased by 7 mm Hg in the WKY, but did not change in the SHR. Moreover, significant decreases occurred in HR, CO and C_m in addition to increases in R_p, Z_c and P_b. These changes between the SHR and WKY were only slight. Atenolol caused decreases in AP, HR and CO in both SHR and WKY, but did not significantly alter the R_p, Z_c, C_m and P_b. Again, the atenolol-induced changes in AP, HR and CO did not appear to be significantly different between SHR and WKY. The results indicate that -adrenergic effects on the heart, Windkessel and resistance vessels are neither greatly enhanced nor impaired during the development of hypertension. In the hypertensive state, significant -adrenergic mechanisms still exert tonic vasodilatory effects on the large and small arterial system.     

Exercise training increases acetylcholine-stimulated endothelium-derived nitric oxide release in spontaneously hypertensive rats

This study investigated the effects of exercise training on the regional release of endothelium-derived nitric oxide (EDNO) in spontaneously hypertensive rats (SHR). Male SHR and Wistar-Kyoto rats were divided into control and training groups, respectively. The training groups received moderate exercise by running on a drum exerciser for 60 min/day, 5 days/week for 10 weeks. At the end of experiments, thoracic aortae and common carotid arteries were excised. Acetylcholine (ACh)-induced relaxing responses due to EDNO release were evaluated in the presence of indomethacin. Vascular relaxing responses to A23187 or to sodium nitroprusside (SNP) were also studied. Our results indicated that after training, (1) the vascular sensitivity of thoracic aortae to ACh-induced relaxation was elevated when indomethacin was present; this effect was absent in the common carotid artery and it was abolished by adding N-nitro-L-arginine, and (2) no significant changes in SNP- or A23187-induced vascular relaxing responses, both being nonreceptor-mediated processes, were observed. We can conclude that for both hypertensive and normotensive rats, exercise training may increase receptor-mediated agonist-stimulated EDNO release in the thoracic aorta, but not in the common carotid artery.