Two possible actions for circulating angiotensin II in the control of vasopressin release

The supraoptic-hypophyseal tract is a primary system for the synthesis and release of vasopressin. Angiotensin II (AII) has been shown to release vasopressin when injected into the cerebral ventricles (IVT). However, intravenous (IV) AII injections have not produced consistent results. The present studies were conducted to examine the effects of AII delivered by either route on the unit activity of supraoptic nucleus (SON) magnocellular neurons. Rats were prepared with intracranial cannulas to insure delivery of drugs to the left lateral ventricle and with polyethylene catheters in the left jugular vein, femoral vein, and femoral artery for systemic injections and arterial pressure recordings. A ventral approach permitted recording from the SON without violating the ventricular-SON partition. Magnocellular neurons were electrophysiologically identified. In the majority of identified cells, IVT AII increased activity. In others pressor doses of AII IV inhibited firing while blood pressure was elevated. After sino-aortic denervation, AII IV excited SON neurons. Based on latency, and the fact that lesioning the anteroventral third ventricle blocked the action of AII IVT, the results indicate that AII IVT acts on a periventricular site to influence SON magnocellular neurons. Furthermore, systemic AII may have two effects on SON neurons: a central excitatory action, and an inhibition due to a baroreceptor reflex.     

A delay recruitment model of the cardiovascular control system

We develop a nonlinear delay-differential equation for the human cardiovascular control system, and use it to explore blood pressure and heart rate variability under short-term baroreflex control. The model incorporates an intrinsically stable heart rate in the absence of nervous control, and allows us to compare the baroreflex influence on heart rate and peripheral resistance. Analytical simplifications of the model allow a general investigation of the rôles played by gain and delay, and the effects of ageing.     

Evaluation of insulin resistance linkage to rat chromosome 4 in SHR of a Japanese colony

The spontaneously hypertensive rat (SHR) is a model of human insulin resistance syndrome. Quantitative trait loci for cellular defects in glucose and fatty acid metabolism have been mapped to an overlapping region of rat chromosome (RNO) RNO4 in SHR of the National Institute of Health colony, where a deletion in the Cd36 gene has been implicated as the causative mutation of insulin resistance. The present study has examined the potential presence of RNO4 linkage to a series of metabolic phenotypes in F(2) progeny derived from SHR of a Japanese colony (SHR/Izm) without the Cd36 mutation. Our data demonstrate that 'major' insulin resistance gene(s) are unlikely to exist on RNO4 in SHR/Izm and in vitro phenotypes measured in isolated adipocytes do not cosegregate in the F(2) population studied. Thus, it seems to be difficult to explain the underlying genetic mechanisms of insulin resistance by a single major gene on RNO4.     

Insertion/deletion polymorphism in clusterin gene influences serum lipid levels and carotid intima-media thickness in hypertensive Japanese females

Clusterin has been implicated in lipid metabolism and atherogenesis, however, the influence of genetic variation has not been examined in Japanese. In this study, we identified 11 single nucleotide polymorphisms (SNPs) of clusterin gene by direct sequencing. Among them, one promoter SNP (-4453T>G), one missense SNP (4183G>A), and 2 common SNPs (5608T>C and 6316delT) were genotyped in 525 asymptomatic hypertensives not treated with lipid lowering agents. -4453T>G, 4183G>A, and 5608T>C showed no correlation with the clinical characteristics, however, in the 6316delT, an insertion (I)/deletion (D) polymorphism, D/D subjects had significantly higher levels of total cholesterol and low-density lipoprotein (LDL)-cholesterol than I/I subjects in females but not in males. Female subjects with the D allele (D/D+I/D) had greater intima-media thickness of the carotid artery than I/I subjects. In a multiple logistic regression analysis, the D allele of 6316delT was detected as an independent predictor for the plaque prevalence. In conclusion, the clusterin gene polymorphism may contribute to the serum lipid levels and the progression of carotid atherosclerosis in hypertensive Japanese females.     

Endogenous ouabain-like factor (OLF) secretion is modulated by nicotinic mechanisms in rat adrenocortical cells

This study tested the hypothesis that rat adrenocortical secretion of endogenous ouabain-like factor (OLF) is regulated by nicotinic mechanisms. OLF secreted by dispersed cell suspensions of zona glomerulosa (ZG) and fasciculata/reticularis (ZFR) cells was found to co-elute with authentic ouabain by reverse phase HPLC; OLF concentrations in cell supernatants were measured by radioimmunoassay. Nicotine (10⁻⁶ − 10⁻³ M) stimulated significant OLF secretion in rat adrenocortical cells. Acetylcholine (10⁻⁷ − 10⁻⁴ M) and eserine (10⁻⁷ − 10⁻³ M) stimulated OLF secretion in ZG cells at lower concentrations and stimulated at higher concentrations. Acetylcholine had no effect on ZFR secretion of OLF, but eserine stimulated OLF secretion. ACTH (10⁻⁸ M) strongly potentiated the OLF stimulatory effect of nicotine in ZG cells; however significant interactions between nicotine and ACTH or angiotensin II on OLF secretion in ZFR cells were not apparent. The ganglionic blockers hexamethonium and mecamylamine further potentiated the effect of nicotine, implicating nicotinic acetylcholine receptors (nAChRs) in regulation of OLF secretion. The α7-receptor antagonist methyllycaconitine (MLA) dose-dependently inhibited the effect of nicotine in the ZG cells, and in ZFR cells MLA potentiated nicotine-induced OLF secretion. These data suggest that nicotinic regulation may underlie OLF secretion by rat adrenocortical cells, and strongly suggest presence of functional nicotinic acetylcholine receptors on these cells.     

Identification and characterization of the mitochondrial membrane sorting signals in phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae

Phosphatidylserine decarboxylase 1 (Psd1p) catalyzes the formation of the majority of phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae. Psd1p is localized to mitochondria, anchored to the inner mitochondrial membrane (IMM) through membrane spanning domains and oriented towards the mitochondrial intermembrane space. We found that Psd1p harbors at least two inner membrane-associated domains, which we named IM1 and IM2. IM1 is important for proper orientation of Psd1p within the IMM (Horvath et al., J. Biol. Chem. 287 (2012) 36744–55), whereas it remained unclear whether IM2 is important for membrane-association of Psd1p. To discover the role of IM2 in Psd1p import, processing and assembly into the mitochondria, we constructed Psd1p variants with deletions in IM2. Removal of the complete IM2 led to an altered topology of the protein with the soluble domain exposed to the matrix and to decreased enzyme activity. Psd1p variants lacking portions of the N-terminal moiety of IM2 were inserted into IMM with an altered topology. Psd1p variants with deletions of C-terminal portions of IM2 accumulated at the outer mitochondrial membrane and lost their enzyme activity. In conclusion we showed that IM2 is essential for full enzymatic activity, maturation and correct integration of yeast Psd1p into the inner mitochondrial membrane.     

16S rRNA技术检测盐诱导 高血压大鼠肠道菌群的变化

目的检测高血压大鼠肠道菌群的变化,探讨正常菌群在盐诱导高血压发生发展中的作用。方法以8%高盐饮食喂养SD雄性大鼠制备高血压模型。Real-time PCR检测菌群结构的改变,同时检测血浆炎性因子IL-1β、IL-6和TNF-α水平变化。结果同对照组大鼠血压(96.00mmHg±5.74mmHg)相比盐敏感组(122.79 mmHg±6.37 mmHg)显著升高,而盐抵抗组无明显变化;实验组大鼠体重(172.00g±15.58g,164.25g±16.11g)较对照组(377.63g±32.47g)明显降低;同对照组相比实验组菌群结构发生比例倒置,即双歧杆菌(6.19±0.47,7.52±0.47 vs 8.59±0.42)、乳杆菌(6.77±0.23,7.09±0.28 vs 7.60±0.26)、拟杆菌(8.98±0.45,8.46±0.47 vs 9.99±0.73)数量降低;肠杆菌(7.93±0.20,7.78±0.29 vs 7.28±0.27)数量升高。同盐抵抗组大鼠相比,盐敏感组双歧杆菌、乳杆菌降低更加显著,但拟杆菌数量高于盐抵抗组。两实验组大鼠血浆细胞因子IL-1β、IL-6和TNF-α水平较对照组均显著升高(P0.05)。结论盐诱导高血压大鼠肠道菌群结构发生改变,盐敏感组双歧杆菌、乳杆菌和拟杆菌含量显著降低,提示其可能参与盐诱导高血压病程。     

SHR和WKY大鼠主动脉hsp 70mRNA水平的比较研究

本工作应用热激蛋白70KD(hsp 70)核酸分子杂交方法,检测了:1.自发性高血压(SHR)主动脉和离体培养的主动脉平滑肌细胞受热激后hsp 70mRNA水平的变化;2.不同细胞培养时间(3个月与6周)的SHR、WKY主动脉hsp 70mRNA水平。结果提示SHR主动脉hsp mRNA水平增加,SHR细胞培养受热激(42℃,15min)后2h,hsp 70mRNA水平明显高于WKY鼠者,6周较3个月的SHR细胞hsp 70mRNA水平高;6周的SHR细胞较同期和3个月的WKY细胞hsp 70mRNA高。推论SHR血管平滑肌细胞对热敏感,原癌基因c-myc和抗癌基因p~(53)可能参与hsp 70表达调控,并共同参与SHR细胞增殖的调节。     

左旋氨氯地平联合综合性心理干预治疗高血压伴围绝经综合征患者的临床观察

目的:探讨左旋氨氯地平联合综合性心理干预治疗高血压伴围绝经综合征患者的临床治疗效果,为临床治疗提供参考。方法:按照随机数字表法将2014年7月-2015年7月三峡大学仁和医院收治的113例高血压伴围绝经综合征患者分为两组,观察组(n=57例)采用左旋氨氯地平联合综合性心理干预,对照组(n=56例)仅予以左旋氨氯地平治疗。治疗1个月后,采用汉密尔顿焦虑量表(HAMA)和抑郁量表(HAMD)评分对两组患者的主要症状改善进行评估,测量两组治疗前后卵巢功能指标促黄体生成素(Luteinizing hormone,LH)、血清促卵泡成熟激素(Follicle stimulating hormone,FSH)以及雌激素(Estrogen,E2),并比较两组患者治疗后的临床疗效。结果:两组患者治疗后的LH、FSH以及E2水平均较治疗前明显改善,且观察组改善的幅度明显优于对照组,差异有统计学意义(P0.05)。两组治疗后的HAMA、HAMD评分均较治疗前降低,且观察组降低的幅度明显优于对照组,差异有统计学意义(P0.05)。观察组治疗后的临床疗效优于对照组,差异有统计学意义(P0.05)。结论:左旋氨氯地平联合综合性心理干预可明显改善患者的负性情绪和提高临床治疗效果,有较高的临床推广价值。     

钬激光电切术对老年高血压患者前列腺增生的疗效及安全性

目的:探讨钬激光和经尿道电切术治疗老年高血压伴前列腺增生的疗效和安全性。方法:回顾性分析2011年1月-2013年1月我科收治的48例患者的临床资料,随机分为两组,每组24例,分别采用经尿道前列腺电切术和激光切除术治疗。观察两组手术时间、术中出血量、住院时间、IPSS和QOL评分及血压变化情况。分别于手术前后应用经直肠超声测量患者前列腺厚度,根据球形体积公式估算前列腺重量。结果:钬激光组手术时间、术中出血量、住院时间明显低于电切组,差异具有统计学意义(P0.05);钬激光组术后前列腺重量、IPSS评分、QOL评分及血压均低于电切组,差异具有统计学意义(P0.05)。结论:经尿道钬激光切除术治疗伴高血压的老年前列腺增生患者安全有效,可在临床推广。