THE EFFECT OF HYPERTENSIVE EPISODES AND CARDIAC HYPERTROPHY ON THE CANINE CARDIAC BAROREFLEX

1. Left ventricular (LV) hypertrophy has been implicated in the reduction of baroreflex sensitivity present in hypertension. The aim of the current study was to investigate the mean arterial pressure-heart rate reflex (MAP-HR) in a model which induced left ventricular hypertrophy but no sustained blood pressure elevation. 2. Five mongrel dogs were exposed to transient blood pressure elevation of between 20 and 30 mmHg, through hindlimb compression using a pneumatic pressure suit, for 7 h per day, 6 days per week for 6 weeks. Resting blood pressure was not altered by the 6 week hindlimb compression intervention. 3. Echocardiographically determined LV mass (mean ± s.e.m.) was 116.0 ± 7.4 g prior to hindlimb compression (baseline) and elevated to 125.4 ± 8.1 g (P= 0.003) after 6 weeks of compression. A reduction in the early (E) to late (A) transmitral diastolic flow ratio (E/A) from 1.80 ± 0.06 at baseline to 1.54 ± 0.09 (P = 0.037) after the 6 week intervention suggested that cardiac compliance was reduced. 4. The maximum gain of the MAP-HR reflex, studied using the ‘steady-state’ drug technique, when blood pressure was normal, showed a trend for reduction from 3.85 ± 0.43 beats/min per mmHg at baseline to 3.10 ± 0.45 beats/min per mmHg (P= 0.067) after 6 weeks of compression. This gain reduction became significant after β-adrenoceptor blockade with propranolol (3.13 ± 0.55 vs 2.32 ± 0.25 beats/min per mmHg; P= 0.039). Covariant analysis showed a significant inverse correlation between LV mass and maximum gain (r= 0.96; P<0.001) during the 6 week compression period. 5. The MAP-HR reflex changes in this model mimic those present in hypertension and implicate cardiac hypertrophy as one possible mediator.     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.     

VASOCONSTRICTOR RESPONSES TO COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM IN CYCLOSPORIN-INDUCED HYPERTENSION IN THE RAT

1. Since plasma renin activity is increased in cyclosporin A (CsA)-induced hypertension in the rat, the role of the vascular renin-angiotensin system (RAS) in CsA-induced hypertension was investigated in rat mesenteric resistance vessels. 2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail-cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001). 3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration-response curves to tetradecapeptide renin substrate (10-¹¹-10^?6 mol/L), angiotensin I (10-^l1-10^?6 mol/L) and angiotensin II (10-¹²-10^?6 mol/L) showed no differences between CsA-treated and control groups. 4. Mesenteric vascular angiotensin-converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA-treated and control rats. 5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA-induced hypertension in the rat.     

高血压大鼠心肌中MMP-2的蛋白表达及其RAS阻断后的变化

[目的]探讨高血压大鼠左室心肌中基质金属蛋白酶-2(MMP-2)蛋白表达的变化以及血管紧张素转化酶抑制剂(ACEI)、血管紧张素Ⅱ1型受体拮抗剂(AT1-ant)单独与联合治疗对高血压大鼠心肌中MMP-2蛋白表达的影响。[方法]40只雄性8周龄的易卒中自发性高血压大鼠(SHRSP)随机分成5组:SHRSP对照组、安慰剂组、缬沙坦组、苯那普利组及缬沙坦与苯那普利联用组。另外,取8只雄性8周龄的京都Wistar大鼠(WKY)作为对照。利用免疫组织化学的方法检测WKY以及SHRSP左室心肌中MMP-2蛋白的表达。[结果]SHRSP的收缩压(SBP)、左室质量指数(LVMI)、胶原容积分数(CVF)、血管周围胶原面积(PVCA)、左室心肌MMP-2蛋白表达较同龄的WKY显著增高。给予苯那普利、缬沙坦单独或联合治疗后SHRSP的LVMI、CVF、PVCA、左室心肌 MMP-2蛋白表达都显著降低。苯那普利、缬沙坦单独应用时的效果没有差异,而联合应用的效果更显著。[结论]SHRSP左室心肌中MMP-2蛋白表达增高,肾素血管紧张素系统(RAS)阻断后MMP-2蛋白表达显著减少;苯那普利、缬沙坦逆转高血压心室重塑的作用可能部分通过下调MMP-2蛋白表达而实现;苯那普利和缬沙坦都能降低SHRSP的血压以及逆转其左室重塑,而联合用药的作用更显著。     

Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia?

Reactive oxygen species: general aspects Reactive oxygen species, including superoxide radicals, hydrogenperoxide, nitric oxide, peroxynitrite, hydroxyl radicals andhypochlorous acid are by-products of normal metabolic processesin cells. Reactive oxygen species can be found in several cellsincluding macrophages and vascular smooth muscle cells. At lowconcentrations reactive oxygen species can act as physiologicalmediators of cellular responses whereas higher concentrationsmay cause cell damage [1,2]. The major sources of reactive oxygenspecies are leakages from the electron transport chains of mitochondriaand endoplasmic reticulum. Cellular energy metabolism is basedon the production of ATP through the electron transport reactionin which O₂ accepts electrons and H⁺ and then is eventuallyreduced to water. Only 1–2% of the electrons are leakedto generate superoxide radicals in reactions mediated by coenzymeQ and ubiquinone and its complexes. During ageing (and probablyin patients     

Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

Hypoxiaisadirectfactorcausinghypoxicpul monaryhypertension (HPH) .hypoxiainduciblefac tor 1α (HIF 1α)isfoundtobethemostcrucialfactorsofarwhichmediatesthecellularresponsetohypoxi a[1] .OurpreviousstudyrevealedthatoverexpressionofHIF 1andendothelin 1(ET 1…     

WHO and ATPIII proposals for the definition of the metabolic syndrome in patients with Type 2 diabetes.

AIMS: Different criteria have been proposed by the World Health Organization (WHO) and by the Third Report of the National Cholesterol Education Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) for the diagnosis of the metabolic syndrome. Its identification is of particular importance for coronary risk assessment. METHODS: The prevalence of the metabolic syndrome was determined according to the two different proposals in 1569 consecutive subjects with Type 2 diabetes. RESULTS: By the WHO proposal, 81% of cases (95% confidence interval, 79-83) were labelled as metabolic syndrome. Microalbuminuria had the highest specificity (99%) and visceral obesity the highest sensitivity (93%). Seventy-eight per cent of patients (95% CI, 76-80) fulfilled the ATPIII criteria for metabolic syndrome, low HDL-cholesterol having the highest specificity (95%), elevated blood pressure having the highest sensitivity. According to both proposals, 1113 patients were positive; 183 were concordantly negative, indicative of a fairly good agreement (k statistics, 0.464). Subjects only positive for the WHO proposal were more frequently males, had a lower BMI and a higher arterial pressure. Only subjects identified by the ATPIII proposal had a significantly higher prevalence of previously detected coronary heart disease. CONCLUSIONS: Minimum criteria for the metabolic syndrome are met in most patients with Type 2 diabetes. Correct identification of the syndrome is important for an integrated approach to reduce the high costs and the associated disabilities. The ATPIII proposal more clearly identifies the burden of coronary heart disease associated with the metabolic syndrome.     

高血压病患者心肌灌注断层显像的相关因素研究

目的探讨高血压病患者心肌灌注断层显像的结果和多种临床因素的关系.方法将97例高血压病患者的心肌灌注断层显像结果同患者的年龄、性别、体重指数、患高血压病的时间、有无抗高血压治疗,有无高血压家族史,患者的血清葡萄糖、肌酐、尿素氮、甘油三酯、胆固醇、脉搏、收缩压、舒张压、脉压差、平均动脉压、患者是否吸烟、饮酒进行非条件Logistic回归分析.结果患高血压病的时间(βi=0.4914,P=0.0017)、吸烟(βi=3.5022,P=0.0176)、高胆固醇血症(βi=1.6147,P=0.0194)是高血压病患者并发心肌缺血的危险因素.结论高血压痛患者戒烟、治疗高胆固醇血症,可降低其并发心肌缺血的风险.