REMODELLING OF THE VASCULAR SYSTEM IN RESPONSE TO HYPERTENSION AND DRUG THERAPY

1. Arterial remodelling is an important mechanism in the pathophysiology of hypertension and its complications, being involved in the decrease of vascular reserve, the autoregulation of cerebral blood flow and the development of atherosclerosis. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth-promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall have been studied in animal models of hypertension. Perindopril completely reversed the aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats and in spontaneously hypertensive rats. The effect of perindopril was consistent with the potent inhibition of vascular ACE, and emphasized the potential role of angiotensin II as a vascular growth modulator. Whether the time constant of remodelling is similar or not in the heart and large vessels remains an important question that requires further investigation.     

RENIN AND ANGIOTENSIN-CONVERTING ENZYME GENOTYPES IN PATIENTS WITH ESSENTIAL HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY

1. The associations between left ventricular hypertrophy (LVH) and specific alleles of the renin and angiotensin-converting enzyme (ACE) genes were studied in patients with essential hypertension and normal blood pressure. 2. LVH was present in 42% of those with essential hypertension (n= 72) and 17% of those with normal blood pressure (n= 44). 3. The frequency of each renin allele was the same in hypertensive and in normotensive patients. Renin allele frequencies were also the same for those with LVH and those with normal cardiac mass. When only hypertensives were considered, renin alleles were in the same proportion for the groups with and without LVH. Similarly, ACE alleles were not associated with essential hypertension nor with elevated cardiac mass. 4. We conclude that, in this population, variations in the renin or ACE genes do not contribute significantly to the development of LVH or to essential hypertension.     

不同年龄组急性心肌梗塞溶栓治疗的对比研究

４７例急性心肌梗塞（ＡＭＩ）患者按发病年龄随机分成三组，进行尿激酶（ＵＫ）溶栓疗效的对比研究。结果表明，１２小时内溶栓的４７例ＡＭＩ患者再通率、死亡率和并发症发生率分别为５５．３％、１４．９％和８．５％。６小时内溶栓再通率老年组（５０％）明显低于青年组（８０％）和老年前期组（７０％）。老年组住院病死率为２５．９％，且有出血并发症发生，而青年组和老年前期组无一例死亡且无一例出血并发症发生。提示ＵＫ溶栓疗效与患者年龄有关，老年人溶栓疗效较差，病死率和出血并发症发生率较高。     

EFFECT OF EXERCISE ON PLASMA ADRENOMEDULLIN AND NATRIURETIC PEPTIDE LEVELS IN MYOCARDIAL INFARCTION

1. We investigated the effect of exercise on plasma adreno-medullin, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and studied the relationship between these peptides and haemodynamic parameters in nine patients with old myocardial infarction (MI) and in eight normal subjects. 2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4 min each and venous blood samples were taken at rest, during each exercise stage and after exercise while monitoring the mean arterial pressure (MAP) and heart rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not significantly increase with exercise. Adrenomedullin levels correlated with PAP and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide levels correlated with LVEDP throughout exercise (P < 0.01) and its increment correlated closely with basal BNP levels at rest (P < 0.01). 4. These results suggest that adrenomedullin does not respond to the acute haemodynamic changes of exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain natriuretic peptide responds to exercise in proportion to the basal synthesis of BNP in patients with left ventricular dysfunction and LVEDP may play a role in increasing BNP during exercise.     

间硝地平对左室肥厚大鼠左室舒张功能及心脑线粒体和血管组织钙含量的影响

用肾性高血压左室肥厚(LVH)大鼠模型,观察了间硝地平(m-Nif)和硝苯地平(Nif)长期给药(ig20mg·kg^-1·d^-1持续9周)对左室舒张功能、左心室肌和大脑线粒体及血管钙含量的影响。与假手术组相比,LVH组左室顺应性明显下降,僵硬度增高,左心室肌和大脑线粒体及尾动脉和主动脉钙含量增加。与LVH组相比,m-Nif和Nif各组左室顺应性改善,僵硬度降低(P<0.01),左心室肌线粒体及尾动脉和主动脉钙含量较LVH组显著降低(P<0.01)。两药在作用强度上无显著差异。     

藻酸双酯钠和甘糖酯对急性心肌梗死患者红细胞变形能力保护作用的机制探讨

为探讨藻藻酯双酯钠(PSS)和甘糖酯(PGMS)对急性心肌梗死(AMI)患者红细胞变形能力(ED)保护作用的机制,检测了52例AMI患者红细胞滤过指数(EFI)、红细胞膜Na~ ,K~ -ATP酶和谷胱甘肽过氧化物酶GSH-Px活性及红细胞膜脂质过氧化物(LPO)的变化,同时观察了PSS和PGMS在体外对ED、Na~ ,K~ -ATP酶、GSH-Px和LPO的影响。结果显示,AMI患者EFI、LPO明显增高,Na~ ,K~ -ATP酶和GSH-Px活性明显降低,与对照组比较差异有极显著性(P<0.001)。AMI患者红细胞与PSS或PGMS在体外温育24h后,EFI、LPO明显降低,Na~ ,K~ -ATP酶和GSH-Px活性明显增高。与温育前比较差异有极显著性(P<0.001),与对照组比较差异无显著性(P>0.05)。提示PSS和PGMS具有保护和提高AMI患者ED的作用,其机制与增强红细胞膜ATP酶和抗氧化酶活性有关。     

甘糖酯,藻酸双酯钠对急性脑梗死患者白细胞变形能力的影响

本文观察了急性脑梗死患者白细胞变形能力的变化及甘糖酯(PGMS)和藻酸双酯钠(PSS)对其影响。结果显示,急性脑梗死患者白细胞IF较对照组明显增高(P<0.001)。白细胞体外孵育2h后,其IF较孵育前明显增高(P<0.001),但加PGMS和PSS孵育的白细胞IF较空白对照管明显降低(P<0.001),且随着药物含量的增加IF逐渐减低,其中以PGMS作有较明显。结果提示,PGMS和PSS具有明显改善白细胞变形能力的作用,对改善急性脑梗死患者微循环,增加缺血脑组织的血流量,缩小梗死面积有重要的意义。     

EFFECTS OF ANGIOTENSINS II AND III ON GLOMERULOTUBULAR BALANCE IN RATS

1. The role of angiotensin as a modulator of proximal glomerulotubular (GT) balance was investigated in anaesthetized rats by examining the relationship between glomerular filtration rate (GFR) and absolute proximal reabsorption (APR) during removal of endogenous angiotensin II (AII) and III (AIII) with enalaprilat (CEI) and then during their subsequent replacement by intravenous infusions. 2. Enalaprilat lowered mean arterial blood pressure (MABP) and increased renal blood flow (RBF), GFR, urine flow rate and sodium excretion. Filtration fraction (FF) was not altered. Absolute proximal reabsorption, derived from fractional lithium clearance, increased by only 48% of the change expected for 'perfect' GT balance. 3. Angiotensin II replacement corrected MABP, GFR and plasma renin level, but reduced RBF and increased FF; APR was decreased and GT balance was restored. Urine flow and sodium excretion remained above control values with AII. 4. Replacement with AIII did not correct the hypotension but completely reversed the renal and renin responses to enalaprilat and restored GT balance without affecting FF. 5. It was concluded that the relation between proximal reabsorption and GFR is considerably modified by the intrarenal angiotensin concentration. The findings are best explained by a direct stimulation of proximal tubular sodium transport by angiotensin at the concentrations existing in anaesthetized rats.     

EFFECT OF TEMOCAPRIL ON HAEMODYNAMIC AND HUMORAL RESPONSES TO EXERCISE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION

1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II). 2. After a 4-week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2–4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment. 3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise-induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment. 4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise-induced increase of plasma NE was significantly suppressed by temocapril. 5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.