Comparative studies on the effects of propranolol and acebutolol on blood pressure, serum lipids and lipoproteins in patients with primary hypertension]

A comparative studies on the effect of propranolol and acebutolol on blood pressure, cardiac function, blood serum lipids and lipoproteins were carried out in 48 patients with the primary hypertension double-blind method was applied. Tested drugs were given for 12 weeks. It was found, that both drugs are potent and comparable hypotensive agents normalizing blood pressure in the majority of treated patients. No significant difference in the effect on heart rate and adverse reactions has been noted. Acebutolol did not change lipid metabolism parameters whereas propranolol slightly but statistically significantly increased serum triglycerides.     

Hypotensive effectiveness and metabolic effects of indapamide in patients with primary arterial hypertension

Indapamide--a non-thiazide diuretic agent--was given to 28 patients with mild and moderate hypertension in a daily dose of 2.5 mg for 12 weeks. Statistically significant decrease in both systolic and diastolic blood pressure and complete normalization of the arterial blood pressure were achieved in 82% of the treated patients. Adverse reactions were mild and transient. However, low but statistically significant decrease in blood serum potassium and changes in the carbohydrate metabolism were seen. No significant effect of the-drug on lipid metabolism was found except the low but statistically significant increase in total cholesterol. Indapamide is an efficient and well tolerated hypotensive agent. However, biochemical indices should be checked up during the treatment due to the potential adverse reactions.     

Comparison of propranolol,metoprolol, and acebutolol on insulin-induced hypoglycaemia.

Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.     

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. A major research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and antimony have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed. An erratum to this article is available at .     

Comparison of the antilipolytic effect of metoprolol,acebutolol, and propranolol in man.

Metoprolol and acebutolol, two supposedly cardioselective beta-adrenoceptor antagonists, were tested in 11 healthy men against propranolol, a non-selective drug, for their effect on plasma free fatty acid concentrations before and after insulin. The fasting concentrations of free fatty acid were significantly reduced after acebutolol and propranolol, and their return to normal after insulin was delayed. Metoprolol had no significant effect on free fatty acid levels either before or after insulin. Although both selective and non-selective beta-blocking drugs should be expected to delay the return of free fatty acid values to normal after insulin, in contrast to propranolol and acebutolol, metoprolol had no such effect. This suggests that metoprolol may not be as effective as the other two drugs in controlling lipid metabolism during long-term treatment with beta-adrenoceptor antagonists.     

Cellular mechanisms of the development of primary arterial hypertension

Modern views on the contraction and dilatation mechanisms of vessel smooth muscle cells are discussed. The data on main role of the cation-transport cell system function peculiarities in the primary arterial hypertension genesis, a relation cell hyperreactivity to those peculiarities and its genetical origin, are reported. It is supposed that the hereditary predisposition forms certain functional lability of cellular elements in different organism tissues, and, in consequence of that, the environmental influences can provoke the development of primary arterial hypertension.     

Pulmonary circulation and right ventricular function in primary arterial hypertension]

Selected parameters of the pulmonary circulation and right ventricular performance were studied in 30 patients with primary arterial hypertension. Four patients belonged to the WHO class I, four to class I/II, 18 to class II and the remaining four to class III. Patients were eligible, if they were in sinus rhythm, without symptoms of left ventricular failure and diseases that night influence pulmonary pressures, and if drugs affecting cardiac performance could be withdrawn safely for 3 days. Ten healthy subjects served as control group. The mean pulmonary capillary wedge pressure and mean pulmonary artery pressure were similar in both groups. In contrast, the systolic pulmonary arterial pressure exceeded 30 mm Hg in 6 patients. Mean pulmonary vascular resistance was higher in examined patients than in the control group. Right ventricular end-diastolic pressure was above 5 mm Hg in as much as 50% of patients. Mean systolic ejection rate showed a tendency to decrease. The results indicate that part of patients with primary arterial hypertension exhibits disorders in the pulmonary circulation and right ventricular performance.     

Atenolol and metoprolol once daily in hypertension.

The effect of once-daily dosage of the two most widely prescribed cardioselective beta-adrenoceptor antagonists used to treat hypertension--namely, atenolol and metoprolol--was studied in nine carefully selected hypertensive outpatients. Each patient received atenolol 50 mg/day, atenolol 100 mg/day, metoprolol 100 mg/day, and metoprolol 200 mg/day in a sustained-release formulation (as Lopresor SR) according to a randomised sequence. After three weeks'' treatment with each drug given once daily comparisons of the treatments 24 hours after dosing showed no important differences between 50 and 100 mg atenolol/day. Metoprolol, as both the standard and the slow-release formulations, had some limitations in controlling systolic blood pressure and heart rate. These results suggest that the recommendations for the treatment of hypertension with these cardioselective beta-adrenoceptor antagonists should be reconsidered since doses smaller than those recommended are almost as effective and much cheaper.     

Increased absorption of zinc from alimentary tract in primary arterial hypertension

Zinc absorption from the alimentary tract, as revealed by serum zinc concentration, was studied in a group of 10 patients (age 37.7±5.1 yr) with moderate and severe untreated primary arterial hypertension before and after a 30-d treatment with perindopril 4 mg/d. Blood pressure was 177.33±16.24/111.33±15.26 mm Hg before and 143.41±17.34/91.29±12.54 mm Hg after treatment (p<0.05/p<0.05). Nine persons (age 37±6.2 yr) with normal blood pressure (121.33±9.9/78±5.23 mm Hg) were the control group. Blood samples were taken from the ulnar vein at 8.00 am (0 h), before taking zinc orally (one tablet of Zincas (zinc aspartate), containing 5 mg Zn²⁺) and at 1, 3, and 6 h after the dose. Serum zinc concentration in control and hypertensive group (before treatment) were initially 15.47±6.26 versus 15.99±5.65 (NS), 19.37±6.40 versus 20.83±4.48 (NS) after 1 h, 17.91±4.76 versus 31.32±10.49 (p<0.003) after 3 h, and 15.32±5.47 versus 17.87±6.56 (NS) after 6 h. Maximal increase of Zn was 4.77±2.10 versus 17.53±4.13, respectively (p<0.001). In the hypertensive group, serum Zn before and after perindopril treatment was initially 15.98±5.65 versus 14.81±3.11 (NS), 20.83±4.48 versus 18.17±2.50 (NS) after 1 h, 31.32±10.49 versus 22.94±5.80 (NS) after 3 h, 17.53±4.13 (p<0.001) after 6 h. Maximal increase of Zn before treatment was 17.53±4.13 versus 9.17±4.67 (p<0.017) after treatment. The following conclusions were reached: (1) In patients with primary arterial hypertension, an increased zinc absorption from alimentary tract was found; (2) A 30-d perindopril treatment 4 mg/d orally decreased zinc absorption in these patients.     

Comparative genetic analysis of different forms of low-renin arterial hypertension

High level of clinical and genetic heterogeneity is a characteristic of arterial hypertension (AH) that is one of the most wide-spread cardiovascular diseases. In most cases (excluding a few monogenic forms), AH is a polygenic disease and genes of renin-angiotensin-aldosterone system play an important role in AH predisposition. 20-25% AH cases occur during low activity of renin in blood plasma (low-renin form of AH) while aldosterone production can be increased (hyperaldosteronism, HA) or normal. We examined polymorphism of genes that code the renin-angiotensin-aldosterone system components in the groups of low-renin forms of AH, namely, primary HA, idiopathic HA and AH with normal level of aldosterone. For all HA cases, the absence of chimeric CYP11B2/CYP11B1 gene that is a cause for monogenic disease--amilial HA of first type, was shown. A comparison of distributions of alleles and genotypes of polymorphous regions of genes: CYP11B2 (C-344T), REN (C-5434T, C-5312T and A BglI G), AGT (Thr174Met), ACE (I/D), CMA (G-1903A), AT2R1 (A1166C) and of their combinations is the groups described above was done. The analysis of carriership of the alleles and genotypes combinations of the polymorphous regions has shown that genes CYP11B2, REN, ACE, CMA andA T2R1 participate in development of low-renin HA. The results are evidence of similarities and some definite differences in genetic nature of the different forms of low-renin AH and, to say more widely, argue that the investigation of genetic predisposition for clinically heterogeneous forms of polygene diseases by comparison of groups of patients, separated in accordance with peculiarities of disease course, holds much promise for their hereditary background understanding.     

Comparative genetic analysis of different forms of low-renin arterial hypertension

Arterial hypertension (AH) ranks among the most widespread cardiovascular diseases and is clinically and genetically heterogeneous. Except for rare monogenic forms, AH is polygenic, and an important role in AH predisposition belongs to genes of the renin-angiotensin-aldosterone system. Low renin activity in blood plasma is observed in 20–25% of AH cases (low-renin form of AH), while aldosterone production can be elevated (hyperaldosteronism, HA) or normal in these cases. Several polymorphisms of the genes coding for the renin-angiotensin-aldosterone system components were studied in patients with low-renin AH forms: primary HA, idiopathic HA, and AH with a normal aldosterone level. The chimeric CYP11B2/CYP11B1 gene, causing monogenic familial HA type 1, was absent from all HA cases studied. The patient groups were compared with respect to the allele and genotype frequency distributions of the polymorphisms of several genes (CYP11B2 (C-344T), REN (C-5434T, C-5312T, and A BglI G), AGT (Thr174Met), ACE (I/D), CMA (G-1903A), AT2R1 (A1166C)), and their combinations. Analysis of the carriership of the allele and genotype combinations implicated CYP11B2, REN, ACE, CMA, and AT2R1 in low-renin HA. The results revealed both similar and different features in the genetic nature of different low-renin AH forms. Investigation of the genetic predisposition to clinically heterogeneous forms of polygenic diseases by comparing patient groups, formed in accordance with peculiarities of the disease course, holds much promise for understanding their hereditary background.     

Neonatal effects of maternal administration of acebutolol.

Systolic blood pressure, heart rate, and blood glucose concentration were measured in the first three days of life in 10 infants born to mothers who had received acebutolol, a cardioselective beta-adrenergic-blocking agent, for hypertension in pregnancy and compared with values in 10 infants whose mothers had received methyldopa. The blood pressure was expressed as a percentage of the expected value. Blood pressure was significantly lower in the infants of the mothers given acebutolol (p less than 0.02, less than 0.01, and less than 0.01 respectively during the three days of observation). Heart rate was also lower, but the significance was only at the 0.05 level. Blood glucose was not significantly different between the two groups. These results suggest that care should be taken in prescribing beta-adrenergic-blocking drugs during pregnancy.     

Urinary zinc excretion is normalized in primary arterial hypertension after perindopril treatment

Increased or unchanged urinary zinc excretion has been reported in hypertension. In the present article, this observation was confirmed in a group of 10 untreated hypertensive patients of both sexes that had no diabetes or obesity. The 24-h zinc excretion was significantly different between the patients: 7.46±3.01 μmol and healthy controls: 5.19±2.19 μmol (p<0.025). After a 1-mo treatment with 4 mg perindopril per day, a decrease of urinary zinc was observed until it reached levels not significantly different from those of the healthy controls (5.98±2.13 μmol). The decrease was significantly different from that of the pretreatment values (p<0.05).