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.     

Effect of nifedipine on plasma renin,aldosterone and catecholamines in arterial hypertension

Summary Acute sublingual administration of nifedipine 10–20 mg to 13 hypertensive patients caused a rapid decrease in blood pressure (BP) and a concomitant increase in heart rate (HR), plasma noradrenaline (NA) and plasma renin activity (PRA); there was no significant change in plasma adrenaline (A) or aldosterone (ALDO). Basal PRA was the major determinant of the rise in PRA, as a close correlation was present between the basal value and the increase caused by nifedipine (r=0.92, p<0.001). The rise in PRA was also correlated with the plasma concentration of nifedipine after 60 min (r=0.80, p<0.01), but it was not correlated with the decrease in BP, the rise in HR or the increase in NA. Nifedipine 30–60 mg daily for 6 weeks caused a reduction in mean BP from 133 to 113 mmHg (p<0.001). Body weight and serum potassium decreased but no consistent change was noted in NA, PRA, ALDO or 24 h-excretion of catecholamines. A significant correlation was present between the change in NA and that in PRA (r=0.74, p<0.01). The alterations in the various parameters in the acute and chronic studies were not correlated. The findings indicate that different regulatory mechanisms are activated during acute and chronic administration of nifedipine. It is suggested that an initial rise in sympathetic activity gradually decreases during prolonged therapy, but it still remains a determinant of PRA.     

Response of blood pressure and plasma norepinephrine to propranolol,metoprolol and clonidine during isometric and dynamic excercise in hypertensive patients

Summary The effects of metropolol (beta₁-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.     

Effect of pinacidil on blood pressure,plasma catecholamines and plasma renin activity in essential hypertension

Summary Pinacidil, a new cyanoguanidine derivative, is an antihypertensive agent with arteriolar vasodilating properties, which acts on precapillary resistance vessels. A trial was carried out in 30 patients with essential hypertension WHO I-II. The treatment period was divided into three phases. Hydrochlorothiazide (HCTZ) and amiloride were administered for 4 weeks in Phase 1 and supine and standing blood pressure decreased significantly. During Phase 2 pinacidil was added to HCTZ/amiloride for the following 3 months. A further significant reduction in blood pressure was obtained. In the next period of treatment (Phase 3) patients were divided into two groups. For 1 month Group A (15 patients) received pinacidil alone and Group B (15 patients) received HCTZ/amiloride. Conventional laboratory blood tests in all patients remained unchanged during treatment. Reported side effects during Phase 2 were headache (2 patients), dizziness (3 patients), palpitations (2 patients) and ankle oedema (2 patients). Plasma renin activity was slightly increased at the end both of Phases 1 and 2. Plasma catecholamines were increased but not significantly at the end of Phase 2 as compared to Phase 1. The results indicate that pinacidil is effective in lowering blood pressure in mild to moderate essential hypertension.     

Effect of oral labetalol on plasma catecholamines,renin and aldosterone in patients with severe arterial hypertension

Summary Arterial blood pressure and plasma catecholamines, renin activity and aldosterone concentration in 12 patients with severe essential hypertension were studied before and after combined -and -adrenergic receptor blockade induced by oral labetalol treatment for 2 months. Furosemide in a fixed dose was employed as a basic antihypertensive agent throughout the study. Blood pressure was adequately controlled in only 6 patients. Mean body weight increased by 1.8 kg and there was a rise in body weight which was inversely correlated with the fall in standing mean blood pressure. The mean plasma noradrenaline concentration decreased from 0.30 to 0.20 ng/ml, whereas plasma adrenaline did not change significantly. Plasma renin activity and aldosterone concentration varied greatly, but the mean values did not change significantly. Change in body weight was correlated inversely with changes in plasma noradrenaline and renin. The results suggest that labetalol, through its combined - and -adrenergic receptor blocking action, induces a rise in body weight, probably due to sodium and fluid retention, which partly counterbalances the antihypertensive effect of labetalol, and partly modifies both renin and sympathetic nervous activity.     

Acute effects of prizidilol on blood pressure,heart rate,catecholamines, renin and aldosterone in essential hypertension

Summary Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (<107 mmHg) from 3 to 7 h and was still below predose levels 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to <95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidilol.     

Changes in blood pressure,heart rate,and sympathetic activity on abrupt withdrawal of tiamenidine (HOE 440) in essential hypertension

Summary A limitation of clonidine therapy is the syndrome of rebound hypertension and sympathetic overactivity after withdrawal. Ten patients, four male, six female, aged 28–64 years, with essential hypertension, were treated for one year with an imidazoline derivative, tiamenidine. Blood pressure fell from an average of 178/108 mm Hg pretreatment to 152/86 mm Hg after 1 year. Tiamenidine was then withdrawn in hospital, replaced by identical placebo under single blind conditions and observations made over 96 h. The study was interrupted in five patients (4 patients within 36 h) because blood pressure rose to greater than 30 mm Hg (systolic) or greater than 20 mm Hg (diastolic) above pretreatment values. For the group, blood pressure was maximal at 194/112 mm Hg, 18 h post withdrawal, significantly higher than pretreatment (p<0.005). Headache, tremor, flushing and insomnia were noted. Saliva production rose 100% at 24 h. Plasma noradrenaline rose within 24 h with an accompanying rise in urinary metanephrine and catecholamine excretion. Tiamenidine appears to share with other imidazolines rebound cardiovascular and autonomic effects following abrupt withdrawal.     

Effect of controlled-release metoprolol on blood pressure and exercise heart rate in hypertension: A comparison with conventional tablets

In a double-blind study with parallel groups a new controlled-release (CR) formulation of metoprolol¹, 100 mg once daily, was compared with conventional metoprolol tablets, 100 mg once daily, in 27 patients with primary hypertension.Exercise tests on a bicycle ergometer were undertaken 24 h after intake of the last dose of the drug following a four-week placebo run-in period and after four weeks of active treatment.     

美托洛尔缓释片对原发性高血压患者心率变异性的影响

目的:研究美托洛尔缓释片对原发性高血压患者心率变异性的影响。方法:94例原发性高血压患者,洗脱2周后,随机口服富马酸美托洛尔缓释片(95 mg.d-1,qd)或酒石酸美托洛尔缓释片(100 mg.d-1,qd)8周。服药前和药后8周行24 h动态心电图检查各1次,分析2组及全部患者的24 h时域和5 min频域指标。结果:2组患者药前、药后的长程时域指标和短程频域指标组间比较均无统计学差异。94例全部患者药前/药后24 h平均心率为(76.27±8.18)/(69.29±6.48)次.min-1(P<0.000 1),药后长程时域指标PNN50显著增加(5.6±4.8)ms vs(8.5±7.2)ms(P<0.000 1);短程频域指标HF增加(88.8±92.8)Hz vs(127.3±127.1)Hz(P=0.007),LF/HF明显下降(2.9±2.0)vs(2.1±2.1)(P=0.002)。结论:美托洛尔缓释片有益于原发性高血压患者心率变异性的恢复,2种不同酸根美托洛尔缓释片的作用无明显差异。     

Effects of acute and long-term beta-adrenoceptor blockade with propranolol on haemodynamics,plasma catecholamines and renin in essential hypertension

Summary The effect of an acute intravenous and repeated oral doses of propranolol on haemodynamics, plasma and urinary catecholamines and plasma renin activity was studied in patients with essential hypertension. Intravenous injection of propranolol 5 mg produced a fall in cardiac output but had no consistent effect on blood pressure. Treatment with oral propranolol for 24 weeks lowered cardiac output and blood pressure; total peripheral resistance did not differ from the pretreatment values. Neither acute intravenous nor chronic oral administration of the beta-blocker affected the resting plasma levels of noradrenaline and adrenaline. Long-term treatment with propranolol reduced urinary excretion of vanilmandelic acid without affecting urinary catecholamine excretion. Acute intravenous injection of propranolol decreased plasma renin activity less than did chronic oral treatment with the drug. The observed time course of plasma renin activity was compatible with the view that suppression of this enzyme contributed to the antihypertensive effect of propranolol.     

针刺治疗对原发性高血压患者血压变异性和心率变异性的影响

目的：探讨针刺治疗对原发性高血压患者血压变异性和心率变异性的影响。方法选择符合条件的60例原发性高血压患者进行针刺治疗,疗程为30 d,采用自身前后对照,分别于治疗前后完善24 h动态血压及24 h动态心电图检查。结果针刺治疗后血压变异性各指标（24 h平均收缩压、24 h平均舒张压、24 h收缩压标准差、24 h舒张压标准差、白昼收缩压标准差、白昼舒张压标准差、夜间收缩压标准差、夜间舒张压标准差）均较治疗前降低,差异具有统计学意义（ P＜0．05）;心率变异性各指标（连续RR间期标准差、平均5 min RR间期标准差、平均5 min RR间期标准差的平均值、连续RR间期差值的均方根值、相邻RR间期大于50 ms的百分数）均较治疗前有所改善,差异具有统计学意义（ P＜0．05）。结论针刺治疗能显著降低原发性高血压患者的血压变异性,改善心率变异性,从而可能改善高血压患者的靶器官损害。     

Effects of low-dose atenolol on postural and postprandial changes in heart rate,blood pressure,venous plasma catecholamines,and plasma renin activity

Summary The administration of a single dose of atenolol 50 mg 1 h before a standard 3100 kJ cold meal in fasting healthy subjects reduced the supine preprandial heart rate and systolic blood pressure, and blunted the postural and postprandial rises in mean heart rate and systolic blood pressure relative to placebo. It did not affect the preprandial supine diastolic blood pressure, nor the postural rise and postprandial drop in diastolic blood pressure.Preprandial administration of atenolol blunted the postural and postprandial rises in mean plasma renin activity, and it enhanced the rise in plasma noradrenaline during eating in the sitting position, and the postprandial concentrations of noradrenaline.The findings do not permit the conclusion that beta₁-adrenergic stimulation was the predminant cause of these atenolol-responsive changes.     

Long term treatment of moderate hypertension with penbutolol (Hoe 893d). I. Effects on blood pressure,pulse rate,catecholamines in blood and urine,plasma renin activity and urinary aldosterone under basal conditions and following exercise

Summary The effects of penbutolol (Hoe 893 d), a new non-selective beta-receptor blocking agent, were studied in 5 patients with moderate hypertension. Initially, it was shown that 2–4 mg given orally once or twice daily tended to lower blood pressure and pulse rate, both at rest and following submaximal work. In prolonged trials (3–8 months) 40–60 mg/day were required to produce an acceptable antihypertensive effect. Penbutolol had no effect on the normal increase in plasma noradrenaline and adrenaline on standing, nor did it alter basal urinary catecholamine excretion. Submaximal work caused no significant change in plasma catecholamines before treatment, but there was a marked rise both in plasma noradrenaline and adrenaline during treatment with penbutolol. In short term studies there was a fall in plasma renin by 4 hours after oral administration of penbutolol 2–4 mg, which persisted for 24 hours. Prolonged treatment with penbutolol 20–30 mg twice daily inhibited renin production under basal conditions and following submaximal work, as well as lowered basal urinary aldosterone excretion. In one patient slight asthmatic symptoms appeared after treatment for 3 months with penbutolol. In other respects penbutolol was well tolerated.     

Long term treatment of moderate hypertension with penbutolol (hoe 893d). II. Effect on the response of plasma catecholamines and plasma renin activity to insulin-induced hypoglycemia

Summary The effect of insulin-induced hypoglycemia on the blood levels of catecholamines and renin activity has been studied in five patients with moderate hypertension before and after treatment for 3 – 8 months with penbutolol (PEN) 20 – 30 mg twice daily. Penbutolol caused no change in fasting blood glucose level. Insulin 0.1 IU per kg body weight i.v. reduced blood glucose concentration by approximately 50 per cent after 30 – 45 min, both before and during treatment with penbutolol. Hypoglycemia prior to medication was accompanied by a marked increase in the production of adrenaline and a minor increase of noradrenaline in all five patients. During treatment the response of adrenaline to hypoglycemia was reduced in four patients and the data was inconclusive in one. Basal renin activity was rather low in three patients, within the normal range in one and relatively high in one. Before penbutolol the hypoglycemia-induced increase in catecholamine production caused no change in plasma renin activity in the three patients with low basal levels, whereas a marked increase was observed in the other two. During medication plasma renin activity remained unchanged on induction of hypoglycemia regardless of the catecholamine response. Despite the marked increase in plasma adrenaline following insulin-induced hypoglycemia, no statistically significant increase in pulse rate was recorded.     

Effect of iloprost on biomarkers in patients with congenital heart disease‐pulmonary arterial hypertension

Some biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin‐1 (ET‐1), asymmetric dimethylarginine (ADMA), galectin‐3 (Gal‐3), B‐type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease‐PAH (CHD‐PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD‐PAH biomarkers and their association with the severity of disease. The effect of iloprost on the regulation of these biomarkers was also studied. A total of 31 patients with CHD‐PAH were enrolled. Seven with positive effects of iloprost (the average reduction in mPAP 11.13±1.73 mm Hg) and 19 with negative effects of iloprost (the average reduction in mPAP 4.21±4.87 mm Hg; iloprost positive group [IPG] vs iloprost negative group [ING], P<.01) and five age‐matched controls were studied. The pulmonary artery blood sample was collected before and after inhaling iloprost, and the plasma concentrations of Gal‐3, ADMA, ET‐1, and NO were measured. A significant positive linear relationship was observed between mPAP and plasma ET‐1, BNP, ADMA, and UA levels in all patients with CHD‐PAH. ET‐1, ADMA, BNP, and UA levels had a significant linear relationship with mean pulmonary arterial pressure, which could be used to predict the severity of CHD‐PAH. ET‐1 might be a potential biomarker to pre‐evaluate the effect of iloprost on CHD‐PAH. Iloprost could affect the expression of Gal‐3 and, therefore, the process of fibrosis could be influenced by iloprost.     

Time course of blood pressure,pulse rate,plasma renin and metoprolol during treatment of hypertensive patients

Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén^®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p<0.001) between the initial (after three doses) and final (after >90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).     

伊贝沙坦对原发性高血压的疗效及心率变异性的影响

目的 :观察伊贝沙坦对原发性高血压 (EH)的疗效及心率变异性的变化。方法 :原发性高血压患者 40例每日口服伊贝沙坦 1 5 0～ 3 0 0mg,共 8wk。观察血压变化 ,记录用药前后 2 4h动态心电图 ,分析心率变异 (HRV)时域和频域指标 ,并与 3 5例健康对照组比较。结果 :①EH患者应用伊贝沙坦后收缩压 (SBP)和舒张压 (DBP)由 2 1 .62± 0 .47/1 2 .0 1±0 .3 2kPa分别下降至 1 8.9± 0 .3 2 /8.0 1± 2 .3 5kPa,有效率达 73 .1 %。②与对照组相比 ,EH患者相邻正常RR间期标准差 (SDNN) ,正常相邻RR间期差值 (RMSSD) ,相邻正常RR间期差值大于 5 0ms的窦性心律 (PNN50 ) ,高频功率 (HF)明显下降 ,低频功率(LF)不变 ,低频功率 /高频功率 (LF/HF)值增加。应用伊贝沙坦后 ,SDNN、RMSSD、PNN50 、HF增加 ,LF/HF值降低。结论 :原发性高血压患者存在HRV下降 ,而伊贝沙坦在有效降低血压同时提高HRV ,改善自主神经功能失衡。     

厄贝沙坦氢氯噻嗪与美托洛尔联合治疗对老年高血压患者血压变异性和心肾功能的影响

目的:探讨厄贝沙坦氢氯噻嗪片联合美托洛尔治疗对老年高血压患者血压变异性(blood pressure variability, BPV)及心肾功能的影响。方法:前瞻性选取110例老年高血压患者作为研究对象,按数字随机表法分为2组：氨氯地平联合组(55例,厄贝沙坦氢氯噻嗪片联合氨氯地平片)及美托洛尔联合组(55例,厄贝沙坦氢氯噻嗪片联合美托洛尔缓释片);选择同期体检的正常老年人55例为正常血压组;比较血压、BPV、心肾功能及炎症指标,评价临床疗效和安全性。结果:美托洛尔联合组总有效率为89.09%。用药8周后,美托洛尔联合组24 h SBP、24 h DBP、24 h SBPV和24 h DBPV较治疗前均显著降低(P<0.01),LVEF明显上升(P<0.05),NT-proBNP、Cys-C、Scr和hs-CRP均显著下降(P<0.05,P<0.01),不良反应发生率为5.46%。上述指标与氨氯地平联合组比较差异无统计学意义。多元逐步回归分析显示,24 h SBPV是NT-proBNP和LVEF的独立影响因素,也是Cys-C和Scr的最大影响变量。结论:厄贝沙...     

Effect of metoprolol on blood glycerol,free fatty acids,triglycerides and glucose in relation to plasma catecholamines in hypertensive patients at rest and following submaximal work

Summary Studies were performed in nine male patients with moderate hypertension. Treatment with metoprolol, 50–150 mg three times daily for 4–17 weeks, had no effect on the plasma level of glycerol, free fatty acids, triglycerides or glucose under basal conditions, neither in the supine nor in the upright position. Submaximal work, performed postprandially, increased plasma glycerol before medication but not during metoprolol, in spite of a marked increase in plasma noradrenaline. The work load employed caused no change in free fatty acids, triglycerides or glucose, neither before medication nor during metoprolol.     

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.