Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

Aims/hypothesis  

Despite advances in pharmacological treatments, diabetes with hypertension continues to be a major public health problem with high morbidity and mortality rates. We recently identified a circulating peptide coupling factor 6 (CF6), which binds to the plasma membrane ATP synthase (ecto-F₁F_o complex), resulting in intracellular acidosis. We investigated whether overexpression of CF6 contributes to diabetes and hypertension by intracellular acidosis.     

The epidemiology of elevated blood pressure as an estimate for hypertension in Aydin, Turkey.

BACKGROUND: Hypertension is an important public health problem, with some variability of its epidemiological properties in different populations. OBJECTIVES: The purpose of this study was to estimate the prevalence of hypertension and to determine the hypertension awareness, treatment and control rates in Aydin, a Turkish province. METHODS: Of 1600 coincidentally selected people aged over 18 years in Aydin, 1480 (92.5%) had their blood pressure (BP) measured and answered a standard questionnaire in 1995. RESULTS: Estimates of the prevalence of hypertension and its control were computed using two different criteria to define hypertension: BP > or =140/90 mm Hg or on treatment and BP > or =160/95 mm Hg or on treatment. Overall, the estimated prevalence of hypertension was 29.6% (for BP > or =140/90 mm Hg or on treatment). Hypertension prevalence increased progressively with age, from 9% in 18- to 29-year-olds to 70.6% in those 70-79 years of age. Women had a significantly higher prevalence than men (34.1% vs 26.0% respectively). Overall, 57.9% of hypertensive individuals were aware that they had high BP, and 82.1% of aware hypertensives were being treated with antihypertensive medications, but only 19.8% of treated hypertensives were under control (systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg). In addition, housewives, unemployed, and the less educated individuals had greater mean systolic and diastolic BP. CONCLUSIONS: Our results indicate that hypertension is highly prevalent in Aydin, Turkey, and the detection and control of hypertension is unsatisfactory.     

Redevelopment of elevated blood pressure following adrenalectomy in rats with isolation-induced hypertension

We have previously shown that rats housed in individual metabolism cages develop arterial hypertension and that this can be prevented by adrenalectomy. In the present work the influence of adrenalectomy on blood pressure, heart rate and on fluid and electrolyte balance was investigated in rats with established isolation-induced hypertension. Seven days after adrenalectomy, systolic blood pressure was reduced to levels similar to those seen before the induction of hypertension; the fall in blood pressure was accompanied by tachycardia. It is likely that the reduction in blood pressure was partly due to volume depletion, since adrenalectomized rats showed reductions in fluid, sodium and potassium balance during the first week after operation. Over the following 3 weeks, blood pressure and heart rate returned to pre-operative hypertensive levels, associated with increasingly positive balances for fluid and sodium. Maintenance of elevated blood pressure in isolated rats following adrenalectomy is likely to have been aided by activation of the renin-angiotensin system, since infusion of saralasin caused profound hypotension in these circumstances, whereas it had a slight pressor effect in intact rats with isolation-induced hypertension.     

Fully automated ambulatory blood pressure in the diagnosis and therapy of hypertension

Technical characteristics of a fully automatic apparatus* for ambulatory semicontinuous blood pressure monitoring are described. Initially, we ascertained the reliability and the fidelity in the reproduction of studied events (blood pressure, heart rate, ECG). Good results were obtained, even in comparison with other methods (blood pressure semiautomatic or invasive monitoring). We then studied the results of the research on 200 hypertensive subjects. The easy applicability of this method allowed us to demonstrate blood pressure variability over a 24-h patient period. We now can evaluate the factors contributing to blood pressure variability and the alterations contributing to the meaning of circadian rhythm. We are now able to comment on the prevalent incidence of organic or neurogenic components in single hypertensive states, the possible coexistence of asymptomatic coronary heart disease, and on the choice and efficacy of hypotensive drugs.     

Cilostazol therapy attenuates monocrotaline-induced pulmonary arterial hypertension in rat model.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by a proliferation of vascular endothelial and smooth muscle cells, resulting in occlusion of the lumen of small pulmonary arteries. Cilostazol, with its antiproliferative effects on vascular endothelial and smooth muscle cells, may ameliorate monocrotaline (MCT)-induced PAH in rats. METHODS AND RESULTS: Male Sprague - Dawley rats (n=10/each group) were randomized to receive MCT (75 mg/kg) only (group 1), MCT plus cilostazol (20 mg .kg(-1 ). day(-1)) (group 2) and saline injection only (group 3). Hemodynamic measurement on day 28 following MCT treatment indicated the development of significant PAH on MCT-treated groups (p<0.0001). Cilostazol was given to group 2 orally on days 28-90. By day 90 following MCT treatment, the right ventricular (RV) systolic blood pressure and RV hypertrophy were significantly higher in group 1 than in groups 2 and 3 (all values of p<0.01). Additionally, connexin43 and endothelial nitric oxide synthase gene expressions of lung and RV, and Bcl-2 protein expression of RV, were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). Furthermore, the number of alveolar sac and small arterioles of the lung were significantly lower in group 1 than in groups 2 and 3 (all values of p<0.01). CONCLUSION: Cilostazol therapy effectively attenuates of MCT-induced PAH.     

Intraduodenal guar attenuates the fall in blood pressure induced by glucose in healthy older adults

OBJECTIVES: Postprandial hypotension occurs frequently in older people and may result in syncope and falls. It has recently been established that the magnitude of the fall in blood pressure is related to the rate at which glucose enters the small intestine. We addressed the hypothesis that the fall in blood pressure induced by an intraduodenal glucose infusion is influenced by the interaction of glucose with the small intestinal absorptive epithelium. METHODS: Eight healthy older participants (four male, four female, age 70.3 +/- 3.4 years) were studied on two separate occasions, in single-blind, randomized order. Participants received an intraduodenal glucose infusion (3 kcal/min) with or without guar gum (4 g) for 60 minutes (0-60 minutes), followed by 0.9% saline intraduodenally for a further 60 minutes (60-120 minutes). Blood pressure and heart rate were measured every 3 minutes. Levels of blood glucose, plasma insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependant insulinotropic-polypeptide (GIP) were also determined. RESULTS: Between t = 0 and t = 30 minutes, the magnitude of the fall in systolic blood pressure (p =.03) and increase in heart rate (p =.027) were lower after guar. The blood glucose (p =.009), plasma insulin (p =.027), plasma GLP-1 (p =.018), and GIP (p <.001) responses to intraduodenal glucose were attenuated by guar. CONCLUSIONS: In healthy older participants, the magnitude of the fall in systolic blood pressure and increase in heart rate induced by intraduodenal glucose are attenuated when the exposure of glucose to the small intestinal mucosa and subsequent glucose absorption is slowed by guar.     

Fasting blood glucose is independently associated with resting and exercise blood pressures and development of elevated blood pressure

OBJECTIVE: To assess whether fasting blood glucose is independently related to blood pressure at rest and during exercise, and to development of elevated blood pressure. DESIGN: Cross-sectional and prospective cohort study of 2014 apparently healthy middle-aged men. METHODS: The baseline survey included carefully standardized blood pressure measurements at rest and during exercise testing, an intravenous glucose tolerance test and a panel of fasting blood tests, including fasting blood glucose. Results from 7-years follow-up provided data on development of elevated blood pressure. RESULTS: Strong associations were found between quartiles of fasting blood glucose and baseline resting and/or exercise levels of blood pressure, and also development of elevated blood pressure over 7 years. Physical fitness, calculated from an exercise test, had a strong modulating effect on blood pressure at all levels of fasting blood glucose. In multivariate models - after adjusting for intravenous glucose tolerance, physical fitness, age, body mass index, triglycerides and cholesterol - fasting blood glucose was strongly associated with blood pressure at rest (coefficient = 2.83, P = 0.0004) and during exercise (coefficient = 6.57, P < 0.0001), and further to development of treated hypertension and/or elevated blood pressure [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.05-1.31]. CONCLUSION: In healthy non-diabetic and non-hypertensive men, strong associations were found between fasting blood glucose and blood pressure at rest and during exercise and to development of elevated blood pressure after 7-years follow-up. Fasting glucose metabolism deserves scrutiny when studying the pathogenesis of hypertension.     

Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model

Although antenatal corticosteroid is recommended to accelerate fetal lung maturation, prenatal dexamethasone exposure results in hypertension in the adult offspring. Since melatonin is a potent antioxidant and has been known to regulate blood pressure, we examined the beneficial effects of melatonin therapy in preventing prenatal dexamethasone-induced programmed hypertension. Male offspring of Sprague-Dawley rats were assigned to four groups (n = 12/group): control, dexamethasone (DEX), control + melatonin, and DEX + melatonin. Pregnant rats received intraperitoneal dexamethasone (0.1 mg/kg) from gestational day 16 to 22. In the melatonin-treatment groups, rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Blood pressure was measured by an indirect tail-cuff method. Gene expression and protein levels were analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. At 16 weeks of age, the DEX group developed hypertension, which was partly reversed by maternal melatonin therapy. Reduced nephron numbers due to prenatal dexamethasone exposure were prevented by melatonin therapy. Renal superoxide and NO levels were similar in all groups. Prenatal dexamethasone exposure led to increased mRNA expression of renin and prorenin receptor and up-regulated histone deacetylase (HDAC)-1 expression in the kidneys of 4-month-old offspring. Maternal melatonin therapy augmented renal Mas protein levels in DEX + melatonin group, and increased renal mRNA expression of HDAC-1, HDAC-2, and HDAC-8 in control and DEX offspring. Melatonin attenuated prenatal DEX-induced hypertension by restoring nephron numbers, altering RAS components, and modulating HDACs.     

N末端前体脑钠肽与老年男性原发性高血压夜间血压升高的相关性研究

目的探讨N末端脑钠肽前体(NT-proBNP)与老年男性原发性高血压夜间血压升高的相关性。方法收入解放军总医院老年心内科2009年1月~2012年12月住院治疗的老年男性原发性非杓型高血压患者590例,分为非杓型组418例和反杓型组172例,收集患者的临床资料,并进行比较分析。结果与非杓型组比较,反杓型组患者年龄较大,肌酐、糖化血红蛋白、NT-proBNP水平较高[(81.47±9.25)岁vs(77.81±11.10)岁,P=0.000;(113.18±99.70)μmol/L vs(93.35±84.49)μmol/L,P=0.017;(7.34±8.35)%vs(6.37±1.05)%,P=0.001;(551.16±991.72)ng/L vs(355.12±934.89)ng/L,P=0.009]。多元回归分析显示,昼间收缩压平均值与NT-proBNP独立相关(B=11.409,P=0.004)。结论反杓型高血压患者节律消失更为明显,靶器官损害更为严重。NT-proBNP与血压的调节有一定的相关性。     

Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity,glucose intolerance,and blood pressure

Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)-alpha gene is involved in the pathogenesis of obesity and obesity-associated hypertension. The aim of the present investigation was to establish whether a segment of rat chromosome 20 (RNO20), which also contains the TNF-alpha gene, determines diet-induced changes in adiposity and blood pressure (BP). The results showed that a transfer of the RNO20 segment from the normotensive Brown Norway (BN) rat onto the background of the spontaneously hypertensive rat (SHR) is associated with a significantly greater increase in adiposity, glucose intolerance, circulating leptin levels, and BP during 12-week, high-fat-diet feeding. In contrast, the transfer is not associated with significant changes in these variables during 12-week, normal-diet feeding. In addition, sequencing of the TNF-alpha gene revealed differences between SHR and BN in the 5'- and 3'-regulatory regions of the gene. Subsequent analyses of TNF-alpha gene expression in fat, muscle, and liver, however, did not provide support for the functional involvement of these differences. In summary, the investigated RNO20 segment contains 1 or more gene variants that affect adiposity, glucose tolerance, serum leptin levels, and BP, but only when the animals are exposed to a particular environment, ie, high-fat-diet feeding. Further studies are needed to identify genes mediating these effects. Considering current changes in our lifestyle involving an increased calorie and fat intake, we believe that gene-environment interactions, such as those described here, play an important role in the current epidemic of obesity and obesity-associated hypertension.     

Cardiac tamponade associated with an elevated arterial blood pressure

A 30-year-old male presented with acute pericarditis and a moderate pericardial effusion. His condition deteriorated suddenly with a marked elevation in blood pressure. The hypertension was erroneously correlated with a low probability of cardiac tamponade, leading to a delay in performing an echocardiogram. The echocardiogram subsequently showed features of cardiac tamponade. Severe elevation of blood pressure in a patient with cardiac tamponade is a rare and under-recognized disorder. This condition is discussed here.     

Hormone replacement therapy and arterial blood pressure in postmenopausal women with hypertension

BACKGROUND: Data on the effect of hormone replacement therapy (HRT) on blood pressure (BP) in hypertensive menopausal women are limited. OBJECTIVE: To investigate the association between HRT and longitudinal change in BP in hypertensive menopausal women. PATIENTS AND METHODS: We recruited a total of 161 hypertensive menopausal women (mean age = 52.2 +/- 6.6 years) attending the hypertension clinic in our hospital that requires HRT to attenuate the effect of menopause symptoms. These women were followed for up tp 36 months, being evaluated every 6 months with measurements of their BP, weight and the number of drugs needed to control their BP. We also measured serum cholesterol levels before and after the initiation of HRT. RESULTS: The systolic BP remained unaffected throughout the whole follow-up period, whereas the diastolic BP was slightly reduced at 6, 24 and 36 months. This decrease was accompanied by an increased need for antihypertensive medication throughout the entire follow-up period, while the body weight also increased at 18, 24, and 36 months. No particular differences were noted with respect to ethnicity, history of pre-eclampsia or surgical menopause, before and after the initiation of HRT. Serum cholesterol levels remained unchanged during the evaluation period. Oestrogen-progestogen combination therapy use was associated with a lower diastolic BP and a smaller number of antihypertensive drugs compared to other forms of HRT. CONCLUSION: HRT use does not have an adverse gross effect on BP in hypertensive menopausal women who need it, although there may be an increased need for antihypertensive therapy during the 36-moth follow-up period of our study.     

Hyperglycemia, glucose intolerance, hypertension and socioeconomic position in eastern Nepal

Abstract. The present study was undertaken to evaluate differences between urban and rural Nepali populations in terms of hyperglycemia, socioeconomic position (SEP) and hypertension, through a community based survey in Sunsari District, eastern Nepal. Blood glucose levels were measured in participants (N = 2,006) S30 years old from urban and rural communities and were classified according to WHO criteria (1998) into normoglycemia (NGY), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and hyperglycemia (HGY). SEP was assessed by structured health interview along with anthropometric measurements and behavioral variables. Hypertension was classified per Joint National Committee (JNC-VII) criteria. Ten point three percent and 11.9% of subjects in this survey (13.3% urban and 11.0% rural) gave a family history and personal history of diabetes mellitus, respectively. Of urban participants (n = 736) with no history of diabetes 70 (9.5%) had HGY and 143 (19.4%) had glucose intolerance (IFG and IGT). Of rural participants (n = 1,270) 114 (9.0%) had HGY and 176 (13.9%) had glucose intolerance. There was an increasing trend in numbers of cases of hyperglycemia and intolerance with increasing age (chi2 198.2, p < 0.001), body mass index (BMI) (chi2 35.1, p < 0.001), SEP (chi2 48.5, p < 0.001) and hypertension (chi2 130.6, p < 0.001). Rural participants had a lower odds ratio [0.706; 95% confidence interval (CI) 0.455-1.096] of having hyperglycemia than urban participants. Individuals with medium and higher SEP had a lower odds ratio (0.878; CI 0.543-1.868) and higher odds ratio (1.405; CI 0.798-2.474), respectively, compared to individuals with lower SEP of having HGY. Both urban and rural populations are at risk for hyperglycemia and glucose intolerance. Individuals having a medium SEP had lower risk of diabetes mellitus than individuals from lower and higher SEP.     

Association between insulin resistance, glucose intolerance, and hypertension in pregnancy

There is an association between insulin resistance, glucose intolerance, and essential hypertension, but the relation between insulin resistance, glucose intolerance, and hypertension diagnosed during pregnancy is not well understood. Transient hypertension of pregnancy, the new-onset nonproteinuric hypertension of late pregnancy, is associated with a high risk of later essential hypertension and glucose intolerance; thus, these conditions may have a similar pathophysiology. To assess the association between insulin resistance, glucose intolerance, essential hypertension, and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension, we performed a prospective study comparing glucose (fasting, 1 and 2 hours postglucose load), insulin, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and triglycerides levels on routine screening for gestational diabetes mellitus. Women who developed hypertension in pregnancy (n = 37) had higher glycemic levels (fasting, 1 and 2 hours postglucose load) on a 100-gram oral glucose loading test, although only the fasting values showed a statistical significance (p < 0.05), and a significantly higher frequency of abnormal glucose loading tests, two hours after glucose load (>or=140 mg/dL) (p < 0.05) than women who remained normotensive (n = 180). Glucose intolerance was common in women who developed both subtypes of hypertension, particularly preeclampsia. Women who developed hypertension had greater prepregnancy body mass index (p < 0.0001), higher frequency and intensity of acanthosis nigricans (p < 0.0001), and higher baseline systolic and diastolic blood pressures (p 相似文献   

胰岛素抵抗大鼠血压升高机制的实验研究

目的:探讨胰岛素抵抗大鼠模型血压升高的机制。方法:通过给予高糖饮食及NG-硝基-左旋-精氨酸-甲基酯(L-NAME)喂养建立不同的胰岛素抵抗大鼠模型,观察大鼠血压及血清内皮型一氧化氮合成酶(eNOS)、一氧化氮(NO)、超氧化物歧化酶(SOD)、超氧阴离子(O2-)和血浆血管紧张素Ⅱ(AngⅡ)的变化。结果:实验前各组大鼠血压差异无统计学意义(P>0.05),而实验4周时,高糖组、L-NAME组的血压均明显高于对照组(均P<0.01)。高糖组(P<0.05)和L-NAME组(P<0.01)NO水平均低于对照组,而O2-升高(均P<0.05)。L-NAME组的eNOS活性低于对照组(P<0.05),高糖组与对照组相比,差异无统计学意义(P>0.05)。与对照组相比,高糖组大鼠血清SOD活性明显降低(P<0.01)。各组大鼠AngⅡ水平与对照组相比差异无统计学意义(P>0.05)。结论:NO水平下降和氧化应激引起NO生物活性降低,在胰岛素抵抗大鼠模型高血压的发病机制中发挥重要作用。