Effects of felodipine on natriuresis, atrial natriuretic factor, the renin-angiotensin-aldosterone system, and blood pressure in essential hypertension

The aim of this study was to evaluate the short-term and long-term effects of felodipine, a new dihydropiridine calcium antagonist, on arterial blood pressure (BP), the renin-angiotensin-aldosterone system, diuresis, natriuresis, and the atrial natriuretic factor (ANF). In 15 essential hypertensives (WHO class II) BP, venous BP at the posterior tibial vein (VBPTV), diuresis, natriuresis, plasma renin activity (PRA), and both plasma aldosterone and ANF levels were evaluated at the end of a washout period and after two and 24 hours and 30, 90, and 180 days of follow-up with felodipine, 5 mg twice daily. The first dose of felodipine induced a significant decrease in BP, which was associated with increases in both heart rate and VBPTV. An acute diuretic and natriuretic effect, increases in ANF and PRA, and a transient decrease in plasma aldosterone levels were also observed. Throughout the follow-up period, the antihypertensive efficacy remained unchanged, whereas variations in electrolyte balance and hormonal parameters quickly disappeared, except for the increase in PRA, which lasted until the 30th day of therapy. In our study, felodipine showed a great antihypertensive activity during both short-term and long-term treatment. Moreover, the effect of the first dose was characterized by transient increases in circulating ANF and decreases in plasma aldosterone concentrations, which were associated with marked diuresis and natriuresis.     

Effects of enalapril maleate (MK-421) on renovascular hypertension

The effects of enalapril maleate (MK-421), a new angiotensin converting enzyme inhibitor, were studied on 5 patients with renovascular hypertension (RVH) due to unilateral renal artery stenosis. The therapeutic dosage was increased when the blood pressure (BP) was not controlled for more than 3 days. Blood sampling was performed before, and 5 hr and 24 hr after the first administration, and on the 3rd day with each dosage. The BP was normalized on 5 mg/day in 1 case, 10 mg in 1 case, 20 mg in 2 cases, and 40 mg plus mefruside in 1 case. Plasma renin activity (PRA) was significantly increased after 5 hr and recovered after 24 hr with 2.5 mg of the enalapril maleate, when the BP was not affected. This indicates that the increase in PRA is likely due to the reduced negative feedback of angiotensin II. When the blood pressure was lowered, PRA was increased and plasma aldosterone concentration (PAC) was decreased significantly. This rise of PRA may depend not only on the reduced negative feedback but also on the fall of BP. It is also considered that the PAC was decreased through the decrease in plasma angiotensin II. A fall of the glomerular filtration rate in one case and also a fall of the perfusion of the kidney of the stenotic side in another case were observed by radioisotope renograms. MK-421 administration was a useful treatment for RVH, and clearly normalized the BP of all the patients studied. However, there was a risk of a fall of renal function on the stenotic side due to the decrease in perfusion pressure.     

Effect of enalapril maleate on vascular endothelial function and platelet-endothelial interactions in patients with essential hypertension

AIM: Evaluation of endothelial function and platelet-endothelial interactions in patients with essential hypertension and dynamics of these changes in the course of treatment with enalapril maleate. MATERIALS AND METHODS: The study included 37 patients with essential hypertension and 22 normotensive volunteers. 17 of hypertensive patients received enalapril maleate (enap, KRKA) 5-20 mg/day during the period of 1.5 months. The complex of investigations included: measurement of total plasma cholesteroi, 12-lead ECG, echocardiography, high-resolution ultrasound investigation of brachio-cephalic arteries, evaluation of flow-mediated dilation, measurement of von Willebrand's factor, spontaneous and induced platelet aggregation. RESULTS: Patients with essential hypertension exhibited higher levels of von Willebrand's factor in plasma and degree of spontaneous and induced platelet aggregation as well as lower responses of vessel wall to hemodynamic stimuli compared to normotensive healthy individuals. There was a strong correlation between endothelial function markers and CAD risk factors, elevation of platelet activity. Treatment with enalapril maleate led to a statistically significant decrease of von Willebrand's factor in plasma and ex vivo platelet aggregation whereas flow-mediated dilatation increased. Values of endothelial function markers and platelet activity approached to those of normotensive subjects and these changes were accompanied by a decrease of ECG signs of left ventricular hypertrophy. CONCLUSION: Patients with essential hypertension were found to have compromised endothelial function. However, the degree of endothelial dysfunction depends not on hemodynamic parameters, but on the cumulative effect of CAD risk factors. Treatment with enalapril maleate may lead to normalisation of endothelial function and decrease of platelet activity.     

Effects of atenolol and enalapril on blood pressure, plasma renin activity and urinary prostanoids

In order to assess whether blood pressure reduction with atenolol or enalapril is associated with changes in renal prostaglandin (PG) synthesis, we studied the effects of 10 weeks therapy in 20 subjects with mild or moderate hypertension. After a four week placebo run-in period, subjects were randomized to receive either atenolol 50-100 mg/day or enalapril 5-20 mg/day for 10 weeks, then crossed over to the alternate active drug. Both drugs lowered blood pressure: placebo 147/97, atenolol 135/87, enalapril 132/87 (p less than 0.05, for both). Atenolol reduced resting heart rate but neither drug changed body weight, serum sodium or potassium or creatinine clearance. Intravenous furosemide was used as a standardized stimulus of renal PG synthesis. Neither drug changed the excretion rates of 6ketoPGF1 alpha or thromboxane B2 (hydrolysis products of PGI2 and thromboxane A2 respectively). Diuretic, kaliuretic, and natriuretic effects of furosemide were also not affected. Plasma renin activity was increased by enalapril but reduced slightly by atenolol. Subjects with more marked blood pressure reduction showed responses to furosemide no different than those with less effect. We conclude that blood pressure reduction with atenolol or enalapril does not change the response of renal eicosanoid synthesis to acute stimulation with furosemide.     

Effects of enalapril on serum lipoproteins in mild essential hypertension

The effect of the angiotensin converting enzyme inhibitor enalapril on serum lipids, apolipoproteins, and lipoproteins was studied in 21 patients with mild essential hypertension. The drug was administered at a dosage of 2.5 to 10 mg daily for 12 weeks. Enalapril significantly decreased the very low-density lipoprotein (VLDL) fraction at eight and 12 weeks. The apolipoprotein (apo) A-I and A-II fractions were significantly increased by 10% and 7.8%, respectively, at 12 weeks. The apo B fraction and the apo B/apo A-I ratio were significantly decreased at eight weeks (8% and 17%, respectively) and at 12 weeks (11% and 19%, respectively). Unchanged were the total cholesterol level, the lipoprotein cholesterol level, the triglyceride level, apo C-II, apo C-III, apo E, and the apo A-I/apo A-II ratio. This study confirmed that enalapril is an effective antihypertensive drug with a favorable effect on the lipid profile.     

原发性高血压合并左心室肥厚对交感神经活性的影响及与血压分级的关系研究

目的 探讨原发性高血压(EH)合并左心室肥厚(LVH)对交感神经活性的影响以及与血压分级的关系.方法 前瞻性选取2019年1月至2020年6月期间广东医科大学附属医院收治的102例EH患者为研究对象,依据超声心动图检查是否合并LVH,分为EH组(n=57)和EH合并LVH组(n=45);依据血压测量水平和高血压分级标准...     

原发性高血压病患者肾素-血管紧张素-醛固酮系统活性的影响因素

目的:探讨原发性高血压病患者血浆肾素-血管紧张素Ⅱ-醛固酮水平的影响因素.方法:原发性高血压病男性患者100例分别按高血压级别、年龄及体质量指数(body mass index,BMI)进行分组,采用放射免疫方法测定立位、卧位血浆肾素活性(plasma renin activity,PRA),血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosteronism,ALD)浓度.采用多元线性回归模型分析年龄、身高、体质量、收缩压、舒张压与原发性高血压病患者血浆PRA,AngⅡ及ALD水平的关系.结果:在高血压病1,2,3级3个亚组间,血浆PRA水平均依次降低(P＜0.05);而AngⅡ及血浆ALD依次升高(P＜0.05).在年龄≤50岁、＞50～60岁和年龄＞60岁3组间血浆PRA,AngⅡ及ALD水平均依次降低(P＜0.05).在BMI≤24 kg/m2,＞24～28 kg/m2和＞28 kg/m2 3组间血浆PRA,AngⅡ及ALD水平差异均无统计学意义(P＞0.05).多元线性回归分析显示收缩压、舒张压为AngⅡ及ALD的正性独立预测因子,而年龄是AngⅡ及ALD的负性独立预测因子;年龄、收缩压、舒张压均是血浆PRA的负性独立预测因子.身高、体质量、BMI与高血压患者血浆PRA,AngⅡ及ALD水平无相关性.结论:高血压病患者存在肾素-血管紧张素-醛固酮系统的过度激活,激活程度主要与年龄、血压有相关性.     

有氧运动对原发性高血压病患者血压、脂代谢及糖代谢的影响

目的:探讨乳酸阈强度的有氧运动对原发性高血压病患者的降压作用;同时观察高血压病患者运动疗程前、后脂代谢及糖代谢的改善程度,以进一步探讨有氧运动对原发性高血压病的康复作用。方法:以递增负荷试验中出现乳酸拐点时的运动强度为训练强度,对11例原发性高血压病患者进行10周的功率自行车训练,观察患者运动前及运动2周、运动10周的血压、血脂、胰岛素、血糖的变化。结果:乳酸阈强度的有氧运动可以明显降低高血压病患者的血压。运动10周后患者的HDL-C和运动前及运动2周时相比均有明显的升高(P<0.01,P<0.001),并且HDL-C/TC及HDL-C/LDL-C的比值也出现了明显的改善(P<0.01)。运动2周患者的胰岛素敏感性出现改善,10周后患者的胰岛素敏感性明显改善(P<0.001)。结论:乳酸阈强度的有氧运动对高血压病患者有降压效果。适宜的有氧运动对胰岛素抵抗作用显著。     

Relations between blood insulin concentration, renin-angiotensin-aldosterone system and clinical picture of hypertension

AIM: To analyse relationships between blood insulin concentration, renin-angiotensin-aldosteron system and clinical picture of hypertension. MATERIALS AND METHODS: Measurements of insulin, renin, aldosteron, angiotensin I, total cholesterol, HDLP cholesterol and triglycerides in the blood were made in 60 males with essential hypertension. The examination also included echo-CG, glucose tolerance test, Ketle's index estimation. RESULTS: Patients suffering from essential hypertension with borderline hyperinsulinemia (insulin within 5.7-12.7 mcU/ml) were characterized by a combination of blood hypertension with a metabolic disorder (obesity or defects in carbohydrate metabolism), activation of renin-angiotensin-aldosteron system and left ventricular diastolic dysfunction. Patients with essential hypertension and marked hyperinsulinemia (insulin exceeded 12.7 mcU/ml) had manifest metabolic syndrome (hypertension, obesity, disturbance of carbohydrate metabolism and hypertriglyceridemia), hyperactivity of renin-angiotensin-aldosterone system, elevated diastolic arterial pressure, remodelling of left ventricular myocardium with development of its concentric hypertrophy and impairment of the diastolic function. CONCLUSION: It is suggested that enhanced activity of renin-angiotensin-aldosterone system may underlie development of insulin-resistance and hyperinsulinemia. The latter plays a significant pathogenetic role in forming clinical picture of essential hypertension in insulin levels > 12.7 mcU/ml.     

Effects of amiloride on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in thiazide-treated hypertensive patients

Total body potassium content, plasma potassium concentration, blood pressure, and plasma concentrations of renin, angiotensin II, and aldosterone were measured in patients with essential hypertension after a run-in period of 8 wk on a regimen of hydrochlorothiazide (median dosage 75 mg/day). Patients were then randomly assigned to continued hydrochlorothiazide therapy (group I) or to receive adjunctive treatment with amiloride (group II, median dosage 15 mg/day or 5 mg per 25 mg hydrochlorothiazide) for the following 3 mo. There were no changes in group I patients during 3 mo on hydrochlorothiazide in plasma potassium, total body potassium content, or the renin-angiotensin-aldosterone system. Blood pressure was also unchanged. In group II patients addition of amiloride to hydrochlorothiazide induced a rise in plasma and total body potassium of approximately 15% and 4%. The potassium-retaining effect was maintained throughout the 12-wk period, although the maximal changes were observed after 8 wk of treatment. Supine blood pressure did not change, but there was a significant decrease in standing systolic blood pressure. There was a marked rise in plasma concentrations of renin, angiotensin II, and aldosterone.     

联合应用波依定和依那普利对单纯收缩期高血压患者动态血压的影响

目的:探讨联合应用波依定和依那普利对单纯收缩期高血压患者动态血压的影响。方法:将120例单纯收缩期高血压患者随机分为3组:波依定组(35例),依那普利组(40例),联合治疗组(45例)。波依定组5 mg、依那普利组10 mg,联合治疗组波依定5 mg 依那普利10 mg 1次/d,共6周。用药前后进行24 h动态血压监测。结果:3组药物治疗第6周末24 h动态血压监测发现,24 h平均收缩压、脉压、舒张压、平均动脉压均较服药前明显降低(P<0.01)。单药波依定组与依那普利组对全天平均收缩压下降幅度分别为(24.6±13.5)mmHg和(23.6±7.3)mmHg,组间差异无统计学意义(P>0.05)。而联合治疗组对全天平均收缩压下降幅度为(31.8±15.4)mmHg,与两单药治疗组相比均有明显降低(P<0.01)。联合组的有效率和达标率较单药治疗组有明显提高(P<0.01),但单药组间差异无统计学意义(P>0.05)。结论:联合应用波依定及依那普利较单独应用波依定与依那普利对单纯收缩期高血压疗效好且安全性好。     

不同时间服用依那普利对血压晨峰现象的影响

目的通过改变依那普利的服用时间来观察其对轻度高血压患者血压晨峰的影响。方法 42例轻度高血压患者给予依那普利10 mg上午(8～12点)服用,4周后监测24 h动态血压以观察白天、夜间和晨起血压情况;如果存在血压晨峰的患者则将依那普利改为晚上睡前服用,剂量不变,1周后再行24 h动态血压监测以观察白天、夜间和晨起血压情况。结果 4周后患者白天血压平均(129±10.5)/(80±6.7)mmHg,夜间血压平均(112±6.2)/(70±4.7)mmHg,晨起血压平均(142±9.5)/(89±5.5)mmHg,85.7%(36例)患者存在血压晨峰现象。改为睡前服用一周后白天血压平均(125±9.5)/(82±5.8)mmHg,与白天服用依那普利比较两者差异无统计学意义(P>0.05);夜间血压平均(110±7.3)/(68±6.6)mmHg,与白天服用依那普利比较两者差异无统计学意义(P>0.05);晨起血压平均(123±7.1)/(79±5.6)mmHg,与白天服用依那普利比较两者差异有统计学意义(P<0.05)。结论轻度高血压患者普遍存在血压晨峰现象,睡前服用依那普利能有效控制轻度高血压患者血压晨峰的发生。     

Effects of dextronatrin on blood pressure, hematocrit, urinary sodium excretion and sympathetic nerve activity of rats

The purpose of this investigation was to study in unanesthetized rats the blood pressure, renal and hematocrit responses to dextronatrin, a structural analogue of atrial natriuretic peptides (ANP). The peptide was infused intravenously for 20 min at doses of either 1 or 20 micrograms/min in binephrectomized rats as well as in rats with intact kidneys. The experiments were started 2 h after preparation of the rats under ether anesthesia. In binephrectomized rats, the small dose of dextronatrin lowered blood pressure and raised hematocrit. In those rats, the larger dose of the investigational peptide had no blood pressure lowering effect, but still increased hematocrit. Dextronatrin had no effect on heart rate, both in rats with and without kidneys. Dextronatrin given at the 1 microgram/min dose to normal rats caused a significant increase in urinary Na excretion. The large dose, however, did not modify this parameter. The effect of dextronatrin (1 microgram/min for 20 min) on splanchnic nerve activity was evaluated in other normal rats after a recovery period of 24 h from surgical procedure. Integrated nerve activity was found to significantly increase in parallel with heart rate while blood pressure was reduced. Taken together, these results show that a low dose of dextronatrin lowers blood pressure and induces an increase in urinary Na excretion and hematocrit. They also indicate that the blood pressure and renal effects of the peptide are abolished when a high dose is administered. In addition, it appears that the shift of fluid from the intra- to the extravascular compartment, reflected in binephrectomized rats by an increase in hematocrit, does not depend on the level of systemic blood pressure. Finally, the present observations suggest that the blood pressure lowering effect of dextronatrin is accompanied in the conscious rat by a stimulation of the sympathetic nervous system.     

Mechanisms of elevated blood pressure in human essential hypertension

This review of the mechanisms of elevation of blood pressure in human essential hypertension first focuses on individual mechanisms and their interrelations. The authors then try to identify those forms of essential hypertension in which the major determinants are known. When the most significant processes associated with elevated blood pressure in individual patients are understood, a rational approach to therapy can be undertaken even though the ultimate cause of the disorder is not understood.     

Elevated sympathetic nerve activity in patients with accelerated essential hypertension.

To determine if an abnormality exists in the sympathetic nervous system of patients with accelerated hypertension, we recorded muscle sympathetic nerve activity (MSNA) from the tibial nerve by microneurography in eight benign essential hypertensives and seven accelerated essential hypertensives. Basal MSNA, plasma renin activity, and plasma angiotensin II levels were significantly higher in accelerated hypertensives than in benign hypertensives (P < 0.05). To clarify the relationship between the renin-angiotensin axis and sympathetic nervous system in the accelerated hypertensives, we measured the MSNA after 7 d of oral administration of captopril (75 mg/d) for antihypertensive treatment in the benign hypertensives and accelerated hypertensives. After administering captopril, the arterial pressure decreased significantly in the benign hypertensives and accelerated hypertensives with decreases in plasma angiotensin II levels, and the decreases in arterial pressure were greater in the accelerated hypertensive than in the benign hypertensives. After captopril administration, the MSNA decreased significantly in the accelerated hypertensives but did not change in the benign hypertensives. Thus, in accelerated hypertensives, sympathetic tone is elevated, and the elevated sympathetic tone is closely related to the activated renin-angiotensin axis tone.     

Differential aspects of the dynamics of the renin-angiotensin-aldosterone system in obesity with and without hypertension and in essential arterial hypertension

This report describes the impulsive function of the RAAS investigated in obese and non-obese hypertensives as compared to obese and non-obese normotensives. The aim of the investigation was to clarify whether or not the hypertensive vascular disease accompanying the ponderal excess can be regarded as a well-defined pathophysiologic entity. Data obtained showed that the behavior of the RAAS in hypertensive obese patients is quite different from that of non-obese hypertensives and obese normotensives. Such a difference implies that hypertension of obese people is a biochemically distinguishable entity. This observation corroborates the concept that the clinical association of obesity-hypertension might be regarded as a syndrome with a proper nosographic dignity.     

纽曼系统护理模式对原发性高血压患者血压及遵医行为的影响

目的探讨纽曼系统护理模式对原发性高血压患者血压控制情况及遵医行为的影响。方法将100例原发性高血压患者随机分为对照组(50例)和观察组(50例)。观察组采用纽曼系统模式,对照组采用全程护理服务模式。比较两组患者血压控制情况及遵医行为的差异。结果观察组患者血压控制效果较好的有47例(94.0%),对照组有30例(60.0%);观察组患者相关知识掌握较好的有39例(78.0%),对照组有30例(60.0%);观察组患者遵医行为优于对照组,两组比较,P<0.05,差异具有统计学意义。结论对高血压病患者实施纽曼系统护理模式,可有效控制和稳定患者的血压,提高患者遵医行为和疾病知识的掌握。