Metabolic effects of long-term angiotensin-converting enzyme inhibition with fosinopril in patients with essential hypertension: relationship to angiotensin-converting enzyme inhibition

Fifty patients with mild to moderate essential hypertension were randomized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to these 16 weeks there was a placebo wash-out period of 2–6 weeks. Blood pressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and after 4 and 16 weeks. Blood lipid status was evaluated at baseline and 16 weeks.The insulin sensitivity index (M/I) increased by 12% during the prolonged placebo period, and subsequently decreased by 12% during treatment with atenolol in that group. A post-hoc analysis of covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry over effects from previous anti-hypertensive treatment. Fosinopril increased glucose disappearance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 at baseline) but had no effect on insulin sensitivity. The change in insulin sensitivity and serum triglycerides during treatment with fosinopril was related to angiotensin-converting enzyme inhibition in serum.In conclusion, carry-over effects from previous anti-hypertensive medication were indicated in this study, probably because of an insufficient wash-out period in many patients. Therefore, 4 weeks of placebo wash-out in all patients is advisable in this kind of investigation.     

Simvastatin inhibits cardiac hypertrophy and angiotensin-converting enzyme activity in rats with aortic stenosis

1. In the present study, we tested the hypothesis that long-term administration of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin may regress hypertrophy and the possible effect of simvastatin on angiotensin-converting enzyme (ACE) activity in rats with pressure-overload cardiac hypertrophy. 2. Pressure-overload left ventricular hypertrophy (LVH) of rats was induced by part coarctation of the abdominal aorta; a sham-operated group served as the control. Six weeks after operation, animals were divided into three groups and an 8 week treatment period was insitgated as follows: (i) the simvastatin treatment group received simvastatin at 3.6 mg/kg per day, p.o.; (ii) the ACE inhibitor group received captopril at 50 mg/kg per day, p.o.; and (iii) the LVH control group received no drug treatment. 3. At the end of the treatment period, left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP) were monitored in vivo. Diastolic pressure-volume relationships were evaluated in a Langendorff preparation with a balloon-in-left ventricle (LV) heart. Myocyte cell width was measured. Angiotensin-converting enzyme activity and angiotensin (Ang)II and hydroxyproline contents of the LV were determined. 4. At the end of the experiments, LVH was established in the LVH control group by increases in LV weight, LV weight/body-weight ratio, LV weight/right ventricle weight ratio, LV myocyte cell width, LVSP and LVEDP by 40, 26, 19, 61, 56 and 59%, respectively (all P < 0.01), compared with the sham-operated group. In the simvastatin-treated and ACE inhibitor groups all these parameters were significantly reduced compared with sham-operated controls. In the LVH control group, ACE activity and AngII and hydroxyproline contents of LV tissue increased by 180, 123 and 70, respectively (all P < 0.01), compared with the sham-operated group. Compared with the LVH group, in the simvastatin-treated and ACE inhibitor groups ACE activity was reduced by 36 (P < 0.05) and 48% (P < 0.01), respectively, AngII content was reduced by 11 (P < 0.05) and 43% (P < 0.01), respectively, and hydroxyproline content was reduced by 23 (P < 0.01) and 10% (P < 0.05), respectively. 5. For the first time, the results of the present study demonstrate that simvastatin significantly reduces LVH, cardiac tissue ACE activity and improves LV performance in pressure-overloaded rats. Because, compared with captopril, simvastatin is more potent in its reduction of LVH and less potent in its inhibition of ACE activity, the mechanism of its antihypertrophic action, in addition to ACE inhibition, may involve inhibition of the mevalonic acid pathway, the main target of action of statins. Thus, HMG-CoA reductase inhibitors may be beneficial for the clinical treatment of cardiac hypertrophy.     

Cardiovascular status following combined angiotensin-converting enzyme and AT1 receptor inhibition in conscious spontaneously hypertensive rats

1. Combined treatment of spontaneously hypertensive rats (SHR) with AT1 receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors has been shown to reduce mean arterial pressure (MAP) more than monotherapy with either agent. The aims of the present study were to investigate the effects of chronic dual renin-angiotensin system (RAS) inhibition using non-hypotensive doses of the AT1 receptor antagonist candesartan cilexetil and the ACE inhibitor perindopril on cardiovascular function and structure. 2. Adult male SHR, aged 15 weeks, were divided into four groups: (i) candesartan cilexetil (0.5 mg/kg per day in drinking water); (ii) perindopril (0.3 mg/kg per day in drinking water); (iii) combined treatment (dual RAS inhibition); or (iv) the appropriate vehicle (0.1% ethanol/0.1% polyethylene glycol/1.5 mmol/l sodium bicarbonate dissolved in water for candesartan cilexetil; distilled water for perindopril). Systolic blood pressure was measured weekly using the tail-cuff method and urinary microalbuminuria was measured fortnightly. 3. After 4 weeks, rats were instrumented for intravenous drug administration and measurement of MAP. At this time, the cardiovascular effects of angiotensin (Ang) I and AngII (5-20 ng) and sodium nitroprusside (SNP) and acetylcholine (ACh; 1-5 micro g) were assessed. In addition, left ventricular : bodyweight and media : lumen ratios were determined as indices of cardiac and vascular hypertrophy, respectively. 4. Candesartan cilexetil and perindopril alone had minimal effect on MAP when measured both directly and indirectly, whereas direct MAP was significantly decreased in the combined treatment group (131 +/- 6 mmHg; P < 0.05) compared with the vehicle group (156 +/- 9 mmHg). Pressor responses to AngI were significantly decreased in all groups compared with the vehicle-treated group and pressor responses to AngII were significantly decreased in the candesartan cilexetil-treated (P < 0.01) and combined treatment groups (P < 0.01) compared with the vehicle-treated group. Depressor responses to ACh and SNP were not significantly affected by any of the antihypertensive therapies compared with vehicle-treated SHR. 5. Vascular hypertrophy was significantly decreased in the candesartan cilexetil and combined groups compared with the vehicle-treated group, whereas cardiac hypertrophy was reduced, with the rank order of effect being: dual RAS inhibition > perindopril > candesartan cilexetil. Urinary albumin tended to decrease with dual RAS inhibition, but was not significantly affected by this short-term treatment. 6. These results demonstrate the efficacy of low-dose dual RAS inhibition as an antihypertensive modality, at least in SHR, not only in reducing arterial pressure, but also in improving cardiovascular structure.     

Effect of angiotensin-converting enzyme insertion/deletion genotype on collagen type I synthesis and degradation in patients with atrial fibrillation and arterial hypertension

Objective: The present study was undertaken to assess the impact of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms on circulating markers of collagen type I synthesis and degradation, and also to study the effect of therapy with ACE inhibitors on these markers in hypertensive patients with atrial fibrillation (AF). Research design and methods: ACE I/D genotypes were assessed in 158 hypertensive patients (71 ± 9 years; 72 male) with AF and 174 patients with arterial hypertension in sinus rhythm (SR) (71 ± 9 years; 88 male). Serum concentrations of amino-terminal propeptide of pro-collagen type I (PINP) and of carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were measured. Results: Of the 332 study participants, 74 (22.3%) were I/I, 158 (47.6%) were I/D and 100 (30.1%) were D/D carriers. Genetic variation in ACE significantly influenced serum CITP levels in AF patients (p = 0.011). CITP levels were lower in D allele carriers (DD and ID) compared with I/I carriers. There was no difference in PINP levels between the different ACE genotype groups (p = 0.302). Patients treated with ACE inhibitors had higher CITP levels compared with those not treated (p = 0.036). Conclusions: This study suggests that the presence of the D allele in hypertensive patients with AF is associated with attenuation of type-I collagen degradation, and that therapy with ACE inhibitors increases degradation of collagen type I. The data indicate a subgroup of patients with AF and arterial hypertension who may benefit to a greater extent from therapy with ACE inhibitors, thus, providing a basis for pharmacogenetics.     

血管紧张肽转换酶抑制剂对高血压病人心脏和大动脉的影响

目的 :评价血管紧张肽转换酶 (ACE)抑制剂对原发性高血压病人心脏和大动脉结构和功能的影响。方法 :应用二维超声、超声心动图及自动脉搏波传导速度 (PWV)测定仪观察 16例采用ACE抑制剂培哚普利治疗 (4mg ,po ,qd ;4wk后若血压 >18.6 / 12 .0kPa ,加服吲哒帕胺 2 .5mg ,po ,qd)的原发性高血压病人心脏、大动脉结构和功能的改变 ,分别在治疗前和治疗 12wk后进行上述检测。结果 :收缩压、脉压、颈动脉 股动脉PWV、颈总动脉内膜 中层厚度和左室后壁厚度在 12wk培哚普利治疗后显著降低 [分别为 (2 0 .4±s 1.4 )kPavs (18.0± 1.2 )kPa ,(7.5± 1.1)kPavs (6 .9± 1.2 )kPa ,(10 .5± 1.3)m·s- 1vs (8.6± 1.0 )m·s- 1,(0 .71± 0 .14 )mmvs (0 .5 9± 0 .14 )mm ,(10 .5± 1.0 )mmvs (9.8± 1.0 )mm ,P <0 .0 1或P <0 .0 5 ];颈总动脉横断面顺应性、容积扩张性在治疗前后无显著性差异(P >0 .0 5 )。结论 :培哚普利对心血管系统的影响不仅仅是与血压降低有关 ,药物引起动脉平滑肌松驰 ,对全身和局部肾素 血管紧张肽系统的抑制能有效地改善高血压导致的心脏、血管结构和功能的改变。     

Effects of intracranial hypertension on steady and pulsatile haemodynamics in dogs

1. Intracranial hypertension (ICH) tends to elicit various cardiovascular changes. Previous studies on the haemodynamic responses to ICH have been confined mainly to measurements of arterial pressure (AP), cardiac output (CO) and total peripheral resistance (TPR). In the present study, we used the technique of arterial impedance analysis for a complete assessment of steady and pulsatile haemodynamics in ICH. 2. In anaesthetized dogs, aortic pressure and flow waves were obtained with high-fidelity Millar sensors. The pressure and flow waves were subjected to Fourier transformation (frequency analysis) for an analysis of impedance spectra. Intracranial pressure (ICP) was elevated by inflation of an epidural balloon. At an ICP of 50 mmHg, the changes in steady and pulsatile haemodynamics were slight. 3. Haemodynamic changes became evident at an ICP of 100 mmHg. The mean AP was elevated by 31 mmHg (+32%) and heart rate (HR) was reduced by 25 b.p.m. (-18%). There was also a significant decrease in CO by 27% and large increase in TPR by 82%. With respect to pulsatile haemodynamics, an elevation of ICP to 100 mmHg caused significant increases in characteristic impedance by 45% and wave reflection by 53%. Arterial compliance was reduced by 50%. The ventricular oscillatory work was increased without a significant change in steady work. 4. The results indicate that ICH causes constriction of resistance vessels to affect AP and TPR. Because the pulsatile haemodynamics reflect mainly the Windkessel functions, ICH also induces stiffness of the large vessels to affect arterial impedance, pulse wave reflection and ventricular oscillatory work.     

The haemodynamic and humoral effects of treatment for one month with the angiotensin converting enzyme inhibitor perindopril in salt replete hypertensive patients

Summary We have studied the effects of treatment for one month with perindopril, 4 or 8 mg once daily, in seven hypertensive patients. Blood pressure was lowered from 164/93 mm Hg to 145/84 mm Hg by 4 mg of perindopril and after one month remained at 142/82 mm Hg. Neither postural hypotension nor tachycardia occurred.Inhibition of plasma angiotensin converting enzyme (ACE) lasting for over 24 h was achieved and there was a significant increase in plasma renin activity (PRA).Maximum plasma concentrations of the active metabolite of perindopril, S-9780, were detected four h after oral administration.After treatment for one month there was evidence of reduced sensitivity of plasma ACE to the action of the inhibitor. The plasma concentration of S-9780 required to produce 50% inhibition of plasma ACE rose from 2.4 ng · ml^–1 following the first dose to 5.5 ng · ml^–1 after one month.     

Imagine how many lives you save: angiotensin-converting enzyme inhibition for atherosclerotic vascular disease in the present era of risk reduction

Introduction: Angiotensin-converting enzyme (ACE) inhibition is clearly beneficial in patients with hypertension, heart failure, and post-myocardial infarction left ventricular (LV) dysfunction. However, whereas initial trials had reported a benefit of ACE inhibition in high-risk vascular patients, current trials of ACE inhibition have failed to demonstrate a clear benefit in vascular patients who are receiving risk-reduction interventions. The purpose of this review is to analyze the reasons behind the failure of the most recent trials of ACE inhibitors in vascular patients without overt LV dysfunction. The reader will gain an understanding of the time-dependent trend towards a reduction in the absolute benefit conferred by ACE inhibition in patients with vascular atherosclerosis as risk reduction interventions are increasingly implemented.

Areas covered: Major trials with a follow-up period of at least 1 year assessing the use of ACE inhibitors in patients with a history of cardiac or vascular events were identified via a PubMed literature search. All-cause and cardiovascular mortality outcomes were reported for each trial, as well as the use of aspirin, lipid-lowering drugs and β-blockers, and the mean LV ejection fraction.

Expert opinion: The findings of recent trials do not support the use of ACE inhibitors in vascular patients who, adherent with risk reduction therapy, do not have hypertension, diabetes, or LV dysfunction.     

Age, hypertension and arterial function

1. Ageing exerts a marked effect on the cardiovascular system and, in particular, the large arteries. Using a variety of techniques to assess arterial stiffness, many cross-sectional studies have demonstrated a significant relationship between age and aortic stiffness, although the age-related changes observed in peripheral arteries appear to be less marked. 2. The relationship between arterial stiffness and hypertension is more complex. The distending, or mean arterial, pressure is an important confounder of measurements of arterial stiffness and, therefore, must be taken into consideration when assessing arterial stiffness in hypertensive subjects or investigating the effect of antihypertensive agents. Current methods for correcting for differences in distending pressure involve pharmacological manipulation, statistical correction or mathematical manipulation of stiffness indices. 3. Many studies have provided evidence that both peripheral (muscular) and central (elastic) arteries are stiffer in subjects with mixed (systolic/diastolic) hypertension compared with normotensive subjects. However, it is unclear to what extent differences in mean arterial pressure explain the observed differences in hypertensive subjects. In contrast, isolated systolic hypertension is associated with increased aortic, but not peripheral artery, stiffness, although the underlying mechanisms are somewhat unclear. 4. Traditional antihypertensive agents appear to reduce arterial stiffness, but mostly via an indirect effect of lowering mean pressure. Therefore, therapies that target the large arteries to reduce stiffness directly are urgently required. Agents such as nitric oxide donors and phosphodiesterase inhibitors may be useful in reducing stiffness via functional mechanisms. In addition, inhibitors or breakers of advanced glycation end-product cross-links between proteins, such as collagen and elastin, hold substantial promise.     

长期应用培哚普利与氨氯地平对高血压病患者左室结构及功能的影响

目的：观察长期应用培哚普利与氨氯地平对高血压患者左室结构及功能的影响。方法：将１２６例原发性高血压病Ⅱ期患者随机分为培哚普利组和氨氯地平组,分别给药２４￣４８月,于服药前后服药后６月、１２月、３６月分别测定右肱动脉血压,心率,左室舒张末内径,舒张期室间隔厚度、左室后壁厚度、左室射血分数、Ｅ峰／Ａ峰比值。结果 两组治疗后血压的明显低于治疗前（Ｐ〈０．０１）;治疗舒张末内径,室间隔厚度,左心室后壁厚度     

老年高血压病患者颈动脉内-中膜厚度的影响因素研究

目的 探讨老年原发性高血压病患者动态脉压、脉搏波传导速度及踝臂指数与颈动脉内-中膜厚度的关系.方法 根据动态血压测量的24h平均脉压(24 h mPP)结果将90例老年高血压病患者分为2组,A组24 h mPP≥60 mm Hg(1 mm Hg =0.133 kPa) (n =45),B组24 h mPP ＜60 mm Hg(n =45).2组患者均采用VP-1000动脉硬化测定仪测量臂踝脉搏波传导速度(baPWV)和踝臂血压指数(ABI),采用HD15100SONO-CT彩色多普勒超声检测仪测量颈动脉内-中膜厚度(IMT).分析24 h mPP、baPWV及ABI与IMT的关系.结果 A组24 h mPP为(65.4±6.6)mm Hg、B组24 h mPP为(51.3±5.0) mm Hg,A组的baP-WV高于B组[(1879±343) mm/s比(1667±32)mm/s]、ABI低于B组[(1.08±0.14)比(1.14±0.09)]、IMT值大于B组[(0.82±0.21)比(0.71±0.16)],差异有统计学意义(P＜0.05).直线相关分析示,24hmPP、baPWV与IMT值呈正相关(r=0.461,P＜0.01;r =0.402,P＜0.01),ABI与IMT值呈负相关(r=-0.267,P ＜0.05).多元逐步回归分析示,24 h mPP、血糖、baPWV是影响IMT的主要因素.结论 老年高血压病患者24 hmPP、baPWV、ABI、血糖与IMT相关,动态血压监测和无创动脉硬化检测可早期预测老年人动脉粥样硬化程度,尽早进行干预治疗,以降低心脑血管事件发生率.     

Angiotensin-converting enzyme inhibition in adult hypertensive rats: a stereological study of renal filtration surface area

1. Angiotensin-converting enzyme (ACE) inhibitor treatment leads to beneficial effects on kidney function. The aim of the present study was to determine whether ACE inhibition at high or low doses affects glomerular capillary surface area and length, glomerular number or total renal filtration surface area in rats with established hypertension and, if so, to determine whether these effects are mediated through bradykinin potentiation. 2. Spontaneously hypertensive rats (SHR) were treated with the ACE inhibitor perindopril at either 3 or 0.1 mg/kg per day (high and low doses, respectively) from 16 to 24 weeks of age. Some rats were concomitantly treated with the bradykinin B2 receptor antagonist S16118 (10 nmol/kg per day). Blood pressure was measured twice weekly during the treatment period. At 24 weeks of age, rats were perfusion fixed at 140 mmHg, the kidneys removed, embedded in resin and examined stereologically to estimate glomerular number and volume, length and surface area of glomerular capillaries and total renal filtration surface area. 3. High- and low-perindopril treatment significantly reduced systolic blood pressure compared with control SHR. However, the rats treated with low-dose perindopril were still considered hypertensive. Neither low-dose nor high-dose perindopril treatment had any observable effect on glomerular number (23 876 +/- 1201 vs 26 240 +/- 1465 glomeruli/kidney, respectively) or volume (2.25 +/- 0.21 and 1.96 +/- 0.06 x 10-3 mm3, respectively) compared with controls (glomerular number 25866 +/- 1210 glomeruli/kidney; glomerular volume 2.24 +/- 0.21 x 10-3 mm3). As a result, there was no significant difference in total renal filtration surface area between any of the experimental groups (8161.6 +/- 550.9, 8699.7 +/- 427.6, 9081.9 +/- 453.6, 8830.2 +/- 521.2 and 8559.4 +/- 341.4 mm2 for SHR, SHR low-dose perindopril, SHR low-dose perindopril + B2 antagonist, SHR high-dose perindopril and SHR high-dose perindopril + B2 antagonist, respectively). Coadministration of the bradykinin antagonist had no observable effect on any of the parameters studied. 4. In conclusion, because neither high-dose nor low-dose perindopril had any effect on total renal filtration surface area, the observed beneficial effects of ACE inhibition on kidney function are not the result of enhancement in glomerular capillary surface area.     

Long-term experience with the combination of clonidine and beta-adrenoceptor blocking agents in hypertension

Summary The risk of cardiovascular and fatal complications and the antihypertensive effect of a clonidine--blocker combination was studied in 98 patients and was compared with the results for a group of patients treated with other antihypertensive regimens. The profile of complications was similar in the two groups for a total follow-up period of more than 2000 treatment-months. Clonidine in combination either with propranolol or atenolol had a distinct antihypertensive effect. However, clonidine plus atenolol resulted in a more immediate and pronounced fall in blood pressure. It is concluded that the combination of clonidine and a -blocker is an effective antihypertensive medication, and that patients treated with it are apparently at no greater risk of serious cardiovascular incidents than are those treated with other regimens.     

臂踝脉搏波传导速度与原发性高血压患者亚临床靶器官损害的关系

目的探讨臂踝脉搏波传导速度与原发性高血压病患者亚临床靶器官损害的关系。方法60例高血压病患者根据臂踝脉搏波传导速度分为正常组24例与增高组36例,所有病例均行头颅磁共振成像、心脏与颈动脉多普勒超声及尿微量白蛋白检查。结果增高组无症状性脑梗死发生率、颈动脉内膜中层厚度、左心室质量指数及尿微量白蛋白均高于臂踝脉搏波传导速度正常组,差异有统计学意义（P〈0．05）。结论臂踝脉搏波传导速度与高血压病患者亚临床靶器官损害有关,对高血压病患者亚临床靶器官损害有良好的预测作用。     

Indices of vascular stiffness and wave reflection in relation to body mass index or body fat in healthy subjects

1. Obesity appears to influence vascular stiffness, an important cardiovascular risk factor. An accurate picture of arterial stiffness may be obtained when a combination of various techniques is used. 2. The purpose of the present study was to assess whether the body mass index (BMI) and body fat content obtained by bioimpedance were of equal value in estimating the influence of body fatness on various indices of vascular stiffness and wave reflection. 3. A total of 175 healthy subjects was studied. Anthropometric measurements and total body bio-impedance analysis were performed to assess fat mass as a proportion of total body composition. Arterial stiffness and wave reflection were assessed using digital volume pulse analysis and tonometric measurement of the wave reflection indices and central haemodynamics. 4. Significant differences in the stiffness index (SI(DVP); P < 0.0001), peripheral augmentation index (pAI(x); P < 0.0001), central augmentation index (cAI(x); P < 0.0001), peripheral pulse pressure (pPP; P = 0.026) and central pulse pressure (cPP; P < 0.0001) were found when the population examined was divided accordingly to tertile of body fat content. However, subdividing various indices of arterial stiffness according to the tertile of BMI did not reveal any significant differences between groups, except for pPP and cPP. 5. Body fat content was significantly correlated with SI(DVP), pAI(x), cAI(x), pPP and cPP. The BMI correlated weakly with SI(DVP), pPP and cPP. 6. In conclusion, the BMI is not very useful in predicting changes in arterial stiffness and wave reflection due to obesity. However, stiffness and wave reflection indices derived from digital volume pulse analysis, the characteristics of radial and aortic pressure waveforms and peripheral and aortic pulse pressure are all related to body fat content, as estimated by bioimpedance.     

Effects of a new long-acting beta-blocker bopindolol (LT 31-200) on blood pressure,plasma catecholamines,renin and cholesterol in patients with arterial hypertension

Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.     

二甲双胍联用抗高血压药物长期治疗对高血压患者胰岛素抵抗和代谢的影响

目的研究二甲双胍联合尼群地平和阿替洛尔长期治疗对高血压患者胰岛素抵抗(IR)和代谢的影响.方法111例轻中度高血压病人,随机分为2组,分别用尼群地平和阿替洛尔联合治疗(A组,n=51)和二甲双胍联合尼群地平和阿替洛尔治疗(B组,n=60),疗程14个月.结果降压总有效率,A组较B组低,但无显著性差异(P＞0.05).A组病人治疗后较治疗前体重增加(P＜0.05),胰岛素敏感指数(ISI)无显著变化(P＞0.05),空腹血糖显著升高(P＜0.001),低密度脂蛋白显著升高,高密度脂蛋白/低密度脂蛋白比显著下降.B组病人治疗后较治疗前,体重无显著变化,ISI显著升高(P＜0.05),血糖、高密度脂蛋白/低密度脂蛋白比和血肌酐显著下降(P＜0.05).二甲双胍联合尼群地平和阿替洛尔治疗能更有效地控制血压,预防体重增加,降低IR,改善血糖代谢和肾功能.结论二甲双胍和抗高血压药物联合应用可能是一组好的药物配伍.     

Early sex differences in central arterial wave reflection are mediated by different timing of forward and reflected pressure waves

Non‐invasive assessment of central arterial pulse wave augmentation has been proved to be useful in predicting cardiovascular adverse events. Previous studies have shown that pre‐pubescent girls had greater central augmentation pressure compared with height‐matched boys. This study sought to investigate which factors contribute to the body height‐independent sexual differences in central arterial wave reflection observed in childhood. This cross‐sectional study involved 819 children and adolescents (6‐18 years of age) of both sexes. Phenotypes of central haemodynamic were obtained by radial applanation tonometry. Heart rate corrected augmentation index (Aix@75) was greater in girls compared with boys (2.9 ± 10.7 vs ?1.7 ± 12.9%, P < .001) as well as the central augmented pressure (cAP; 1.3 ± 3.3 vs 0.1 ± 3.8 mm Hg, P < .001), even adjusting for age, heart rate and body height. Left ventricular ejection duration (ED) was longer (320 ± 26 vs 314 ± 24 ms, P = .004) and time to inflection point (Tr) was shorter in girls (139 ± 14 vs 141 ± 21 ms, P = .014). The reduction of Aix@75 with increasing body height was steeper in boys (?0.499 ± 0.030 vs ?0.428 ± 0.036%/cm, P < .001) as well as the reduction of cAP with increasing body height (?0.108 ± 0.010 vs ?0.066 ± 0.013 mm Hg/cm, P < .001). Body height‐independent sexual differences observed in the pulse wave reflection indices from early adolescence were mediated by different timing of forward and reflected pressure waves.     

Antagonizing bradykinin (BK) obliterates the cardioprotective effects of bradykinin and angiotensin-converting enzyme (ACE) Inhibitors in ischemic hearts

Bradykinin (BK) (1 × 10 ^?12?1 × 10^?8 mol/l) and the ACE inhibitor ramiprilat (2.58 × 10 ^?9?2.58 × 10^?5 mol/l) markedly reduced the incidence and duration of reperfusion arrhythmias in the isolated ischemic rat heart. Pretreatment with ramipril (1 mg/kg p.o.), enalapril (10 mg/kg p.o.), but not captopril (50 mg/kg p.o.) had similar effects. Active compounds also improved cardiodynamics and reduced lactate dehydrogenase (LDH) and creatine kinase (CK) activities, as lactate formation in coronary venous effluent. Cardiac tissue levels of glycogen, adenosine triphosphate (ATP), and creatine phosphate (CP) were preserved. The BK antagonist D-Arg-[Hyp², Thi^5,8, D-Phe⁷]BK abolished the beneficial effects of BK, ramipril, and ramiprilat in a competitive way. Increased concentrations of BK or ramiprilat were able to reverse the antagonism. In anesthetized dogs an infusion of BK, at the dose of 1 ng/kg/min during coronary occlusion and reperfusion was devoid of cardiovascular effects but reduced mortality and the decrease of LDH activity and lactate concentration in coronary sinus blood and preserved tissue levels of glycogen and energy-rich phosphates in the ischemic myocardium.     

Estimation of arterial mechanics in clinical practice and as a research technique

1. Large conduit artery pathophysiology is associated with considerable morbidity with even normal ageing, irrespective of concurrent influences, associated with impaired arterial function. 2. Recent technical advances have enabled high-resolution non-invasive assessment of pulsatile arterial properties, but this has been largely confined to more muscular superficial arteries. There has been less study of arterial regions prone to disease that would, theoretically at least, benefit from pharmacological or other intervention to improve function. 3. Based on studies in animal models and, in particular, human arterial segments, specific pharmacological agents have been proposed as improving arterial behaviour. If this is to become a therapeutic target, it behoves increased effort to understand and measure meaningful indices of arterial function and to find ways of assessing response and outcome. 4. A number of different approaches to assessment and quantification of arterial mechanics are available in the literature. The present review compares and discusses some of these different techniques and looks at differences between arterial segments and evidence that appropriate intervention may beneficially modify arterial behaviour. 5. For clinical or research usefulness, assessment of arterial mechanics must provide more information than currently derived from simple numerical measurement of brachial blood pressure. This is particularly true because epidemiological risk evidence is based on brachial rather than central blood pressure recordings. There has been an explosion of work in this field in recent years and the present review does not pretend to reference all relevant material; rather, it tries to provide a broad coverage of the topic and hopes to support the need for continued endeavours in the field of arterial mechanics.