Biochemical mechanisms involved in the beta-blocker-induced changes in serum lipoproteins.
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Adenylyl Cyclase Inhibitors↗
Biomedical subjects
P Lijnen
Publications and source records attributed to P Lijnen.
A meta-analysis of outcome trials in elderly hypertensives.
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Aged↗
Erythrocyte membrane lipids and cationic transport systems in men.
OBJECTIVE: The relationship between erythrocyte membrane and plasma lipids and various transmembrane erythrocyte cationic fluxes was examined in 53 normal men. DESIGN: Different measurements of erythrocyte transport systems were obtained: Na(+)-Li+ countertransport activity; Na+, K+ cotransport activity; Na+, K(+)-ATPase pump activity and the ground membrane permeability for Na+ and K+ as well as the intra-erythrocyte Na+, K+ and Mg2+ concentrations. Plasma cholesterol, triglycerides, phospholipids, free fatty acids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane contents of cholesterol, phospholipids and free fatty acids were obtained from fasting subjects. RESULTS: In single regression analysis the erythrocyte Na(+)-Li+ countertransport and Na+, K+ cotransport activities were negatively related to the erythrocyte membrane cholesterol, phospholipids and free fatty acids contents. The Na+, K(+)-ATPase pump activity as assessed by the ouabain-sensitive Na+ efflux was also inversely related to the membrane cholesterol and phospholipids contents. In multiple regression analysis the red blood cell Na(+)-Li+ countertransport activity was independently and negatively related to the membrane cholesterol and free fatty acids contents. CONCLUSION: Our data show that an elevated level of erythrocyte membrane lipids in normal men is accompanied by lower Na(+)-Li+ countertransport, Na+, K+ cotransport and Na+, K(+)-ATPase pump activities.
Adult↗
Comparison of the effect of celiprolol and nifedipine on blood pressure and plasma lipids.
During a double-blind, randomized study in hypertensive patients, changes in blood pressure (BP) and in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily) each time using a double dummy technique. After 6 weeks, dosages of each drug could be doubled. Both drugs caused similar reductions in blood pressure but after 12 weeks treatment, the percentage of decrease in diastolic BP (DBP) was more pronounced (p less than 0.01) in the nifedipine group (-18%) than in the celiprolol group (-12%). After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks treatment were different (p less than 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified, suggesting that reverse cholesterol transport was not affected by the drugs. In both treatment groups, a significant positive relationship was observed between changes in LDL cholesterol and apoprotein B. As compared with nifedipine, celiprolol after 12-week therapy had a rather favorable plasma lipid profile. The clinical relevance of such findings, in terms of prevention of cardiovascular complications, has yet to be established.
Acyltransferases↗
Determinants of serum zinc in a random population sample of four Belgian towns with different degrees of environmental exposure to cadmium.
This report investigated the distribution of serum zinc and the factors determining serum zinc concentration in a large random population sample. The 1977 participants (959 men and 1018 women), 20-80 years old, constituted a stratified random sample of the population of four Belgian districts, representing two areas with low and two with high environmental exposure to cadmium. For each exposure level, a rural and an urban area were selected. The serum concentration of zinc, frequently used as an index for zinc status in human subjects, was higher in men (13.1 mumole/L, range 6.5-23.0 mumole/L) than in women (12.6 mumole/L, range 6.3-23.2 mumole/L). In men, 20% of the variance of serum zinc was explained by age (linear and squared term, R = 0.29), diurnal variation (r = 0.29), and total cholesterol (r = 0.16). After adjustment for these covariates, a negative relationship was observed between serum zinc and both blood (r = -0.10) and urinary cadmium (r = -0.14). In women, 11% of the variance could be explained by age (linear and squared term, R = 0.15), diurnal variation in serum zinc (r = 0.27), creatinine clearance (r = -0.11), log gamma-glutamyltranspeptidase (r = 0.08), cholesterol (r = 0.07), contraceptive pill intake (r = -0.07), and log serum ferritin (r = 0.06). Before and after adjustment for significant covariates, serum zinc was, on average, lowest in the two districts where the body burden of cadmium, as assessed by urinary cadmium excretion, was highest. These results were not altered when subjects exposed to heavy metals at work were excluded from analysis.
Adult↗
Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study.
This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.
Adult↗
Cellular and humoral effects of naftopidil in man.
The effects of naftopidil on the intracellular concentration and transmembrane fluxes of Na+ and K+ in erythrocytes and on the intracellular Na+, K+ and free cytosolic Ca2+ concentration in platelets were studied in twenty-four normal male subjects, using a double-blind study design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 8) or naftopidil 25 mg (n = 8) or 50 mg (n = 8) once a day for 4 weeks. Intraerythrocyte Na+ concentration and the erythrocyte anion carrier were decreased during naftopidil administration. No significant effect of naftopidil could be demonstrated on ouabain-sensitive Na+ efflux, bumetanide-sensitive Na+ efflux, ouabain, bumetanide-resistant Na+ and K+ efflux and Na+, Li(+)-countertransport activity in red blood cells or on the intraerythrocyte K+ and Mg2+ concentration. The free cytosolic Ca2+ and Na+ concentration in platelets was also decreased during naftopidil administration while no effect of naftopidil was found on the intracellular K+ and Mg2+ concentration in platelets.
Administration, Oral↗
Mean and range of the ambulatory pressure in normotensive subjects.
To perform a meta-analysis of published reports in an attempt to determine the mean and range of normal ambulatory blood pressure (BP), 23 studies including a total of 3,476 normal subjects were reviewed. Most studies were compatible with a mean 24-h BP in the range of 115-120/70-75 mmHg, a mean day time BP of 120-125/75-80 mmHg, and a mean night time BP of 105 to 110/60 to 65 mmHg. With weighting for the number of subjects included in the individual studies, the 24-h BP averaged 118/72 mmHg, the day time BP 123/76 mmHg, and the night time BP 106/64 mmHg. The night/day pressure ratio averaged 0.87 for systolic and 0.83 for diastolic BP, with ranges across the individual studies from 0.79 to 0.92 and from 0.75 to 0.90, respectively. If the mean +/- 2 standard deviation interval in the various studies was considered normal, the range of normality was on average 97 to 139/57 to 87 mmHg for the 24-h BP, 101 to 146/61 to 91 mmHg for the day time BP, and 86 to 127/48 to 79 mmHg for the night time BP. Until the results of prospective studies on the relation between the ambulatory BP and the incidence of cardiovascular morbidity and mortality become available, the aforementioned intervals, which summarize the experience of 23 investigators, could serve as a temporary reference for clinical practice.
Adolescent↗
Review of the major hypertension trials in the elderly.
The different intervention trials in elderly hypertensives are compatible with the hypothesis that hypotensive drug treatment can decrease cardiovascular mortality mainly by decreasing cerebrovascular mortality. A decrease in the fatal and nonfatal cardiovascular event rate is mainly due to a decrease in cerebrovascular events. It is not established whether hypotensive drug treatment is advisable in symptomless patients with isolated systolic hypertension and in patients with uncomplicated hypertension above age 80. A sudden reduction in blood pressure should be avoided, but whether a progressive reduction of systolic blood pressure below 140 mmHg and of diastolic blood pressure below 85 mmHg is dangerous or advantageous remains to be established.
Aged↗
Hormonal effects of the diuretic xipamide in healthy men.
The effect of xipamide on plasma alpha-atrial natriuretic peptide and the renin-aldosterone-kallikrein system have been studied in 12 healthy men, using a double-blind cross-over design. After a run-in period on placebo of 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once daily (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The plasma concentration of alpha-atrial natriuretic peptide fell after 1 week of xipamide administration and increased during prolonged xipamide administration but remained reduced. The changes in plasma alpha-ANP observed after 1 week of xipamide were negatively correlated with the changes in hematocrit and hemoglobin. Plasma renin activity (PRA), aldosterone concentration (PAC), and urinary excretion of aldosterone and kallikrein increased after 1 week of xipamide administration, levelled off during the second and fourth weeks, but remained elevated during further prolonged xipamide administration for 16 weeks. The xipamide-induced changes in PRA and PAC were positively correlated with the changes in the hematocrit and hemoglobin. The changes in plasma renin, aldosterone, and alpha-atrial natriuretic peptide during xipamide administration may be related to diuretic-induced volume contraction.
Adult↗
Effect of antihypertensive medication on endurance exercise capacity in hypertensive sportsmen.
Beta-adrenoceptor blockade can influence exercise capacity negatively, but data on the effect of converting enzyme inhibition and of calcium entry blockade on exercise capacity in hypertensive sportsmen are scarce. This report deals with the effect of the various types of antihypertensive medication on endurance exercise capacity in 14 hypertensive sportsmen, aged 39 +/- 3 years and weighing 73 +/- 2 kg (mean +/- s.e.m.). The patients were treated for 3 weeks with either placebo, atenolol (50 mg/day) enalapril (10 mg/day) or verapamil (240 mg/day) following a double-blind randomized cross-over design. At the end of each treatment period, they performed an endurance exercise test on the bicycle until exhaustion at 70% of their previously determined exercise capacity. Venous blood was sampled before and after exercise. In comparison with placebo, total exercise duration was not affected by enalapril (-3 +/- 7%) or verapamil (-7 +/- 11%). During treatment with atenolol, two patients had to interrupt their intake of the beta-blocker because of side effects. In the 12 remaining subjects, exercise duration was significantly decreased by 38 +/- 12% (P less than 0.01). Atenolol also induced decreases in plasma-free fatty acid concentration before and after exercise and an increase in potassium concentration after exercise, whereas enalapril and verapamil did not induce metabolic changes. During exercise, systolic blood pressure was decreased by atenolol (P less than 0.001) and enalapril (P less than 0.01) and diastolic blood pressure by enalapril (P less than 0.001), verapamil (P less than 0.05) and atenolol(P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of cadmium on transmembrane Na+ and K+ transport systems in human erythrocytes.
The effects of cadmium (Cd2+) on Na+,K(+)-ATPase in disrupted human erythrocyte membranes and on various transmembrane Na+ and K+ transport systems in intact erythrocyte suspensions were studied. Cadmium2+ inhibited the erythrocyte Na+,K(+)-ATPase enzyme with a 50% inhibition at a Cd2+ concentration of 6.25 microM. The Cd2+ inhibition in the human erythrocyte was non-competitive with respect to Na+,K+, and ATP. Cadmium2+ exerted no acute effect, however, on the Na+,K(+)-ATPase pump activity as measured by the ouabain sensitive 86Rb uptake or Na+ efflux in intact red blood cells. Cadmium2+ also inhibited the Ca2+ dependent K+ channels in human red blood cells, whereas it had no effect on Na+,K+ cotransport, Na+,Li+ countertransport, anion carrier, and the number of active Na+ pump units. The data indicate that in human erythrocytes under acute conditions Cd2+ exerts an inhibitory effect on Na+,K(+)-ATPase enzyme in disrupted erythrocytes and the Ca2+ stimulated K+ efflux in intact red blood cells without affecting the Na+ pump, Na+,K+ cotransport, and Na+,Li+ countertransport activity.
Biological Transport, Active↗
Effect of prostaglandin inhibition by indomethacin on plasma active and inactive renin concentration in men.
The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (p = 0.004), total (p less than 0.001), and inactive (p = 0.02) renin at rest recumbent on average by 42, 19, and 8%, respectively, and at rest sitting on average by 45, 15, and 3%, respectively. Inhibition of prostaglandins with indomethacin reduced (p less than 0.001) active and total renin at each level of work load but not (p = 0.32) inactive renin. However, the exercise-induced stimulation (p less than 0.05) of active and total renin still occur during indomethacin. Indomethacin reduced (p less than 0.001) at rest sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2 by 50 and 54%, respectively, prostaglandin F2 alpha by 36 and 39%, respectively, and 13,14-dihydro-15-keto-prostaglandin F alpha by 38 and 60%, respectively. The urinary excretion of immunoreactive prostaglandin E2 and F2 alpha was also reduced.
Adult↗
The association between blood pressure, calcium and other divalent cations: a population study.
This report investigated the associations between blood pressure and the levels of various divalent cations in blood and urine in the population at large. The 1,982 participants (963 men and 1019 women; mean age 48 years) constituted a stratified random sample of the population of 4 Belgian districts. Systolic/diastolic pressure averaged 133/78 mmHg in men, and 128/76 mmHg in women. Serum total calcium (2.37 mmol/l), serum magnesium (1.00 mmol/l) and blood cadmium (10.0 nmol/l) were on average similar in the two sexes. By contrast, serum zinc (13.1 and 12.6 mumol/l, respectively), blood lead (0.56 and 0.36 mumol/l) and the urinary excretions of calcium (4.86 and 3.95 mmol/24h), copper (0.16 and 0.13 mumol/24h), and cadmium (9.4 and 7.2 nmol/24h) were significantly higher in men than in women. After adjustment for significant blood pressure covariates (age, body mass index, pulse rate, log gamma-glutamyltranspeptidase, smoking habits, and in women the contraceptive pill), serum total calcium was independently and positively correlated with systolic pressure in both sexes, and with diastolic pressure in women. After similar adjustments systolic pressure was positively correlated with urinary copper in men and women. In addition, systolic pressure and blood lead, and diastolic pressure and urinary cadmium were negatively correlated in men. In conclusion, this population study demonstrated a positive relationship between systolic blood pressure and both serum total calcium and urinary copper.
Adult↗
Ambulatory blood pressure monitoring in clinical trials.
Monitoring ambulatory blood pressure, instead of taking pressure readings in hospital, avoids the so-called white-coat effect and allows more readings to be obtained over a longer period of time. It improves the accuracy of the blood pressure estimate and increases the statistical power of therapeutic trials for hypertension. Subjects with white-coat or office hypertension can be detected by ambulatory blood pressure monitoring and excluded from clinical trials. In 23 studies, including a total of 3304 normotensive subjects, the 24-h ambulatory blood pressure averaged 118/72 mmHg; the daytime and night-time pressures were 123/76 mmHg and 106/64 mmHg, respectively. If the mean plus two standard deviation (s.d.) interval is considered the upper limit of normal, the meta-analysis suggested that hypertension may be suspected if the 24-h pressure exceeds 129/87 mmHg, or if the daytime or night-time pressures are higher than 146/91 mmHg or 127/79 mmHg, respectively. On balance, most studies suggest that placebo effects on blood pressure are not observed when blood pressure is measured with ambulatory recorders. If confirmed, this observation indicates that it is possible to simplify the design of trials in the field of hypertension. Ambulatory blood pressure readings should be obtained with properly validated monitors. If the recordings are of sufficient quality, editing does not increase the precision of the subsequent statistical analyses. The statistical analyses should account for diurnal rhythms, and subject and treatment effects.
Antihypertensive Agents↗
[Hemodynamic effects of urapidil in men].
In hypertensive patients as well as in normal subjects, urapidil has a hypotensive action. This is mainly mediated by a peripheral alpha adrenoceptor blockade with a decrease in systemic vascular resistance. In addition, acute animal experiments demonstrated a centrally mediated hypotensive action, possibly by 5-hydroxytryptamine1A-receptor stimulation. Studies in humans showed an increase in cardiac output, which was not always significant; it resulted either from an increased heart rate or an increased stroke volume. Acute changes in pulmonary hemodynamics after administration of urapidil were most pronounced in patients with pulmonary hypertension: pulmonary artery pressure and pulmonary vascular resistance decreased significantly and pulmonary capillary wedge pressure decreased non-significantly. A small reduction in pulmonary artery pressure and capillary wedge pressure was seen in patients with congestive heart failure and in patients in whom acute blood pressure elevation developed after coronary bypass surgery. In patients with essential hypertension, forearm, renal and splanchnic flows were shown to increase and vascular resistance to decrease significantly after an acute intravenous doses of urapidil. The hemodynamic changes that occur during chronic therapy are largely unknown, except for systemic vascular resistance which remains decreased.
Antihypertensive Agents↗
[Converting-enzyme inhibitors in the treatment of elderly hypertension patients].
According to this review of available data on converting enzyme inhibitors in elderly hypertensives, the drugs' hypotensive action has been clearly established and seems to be similar in degree to that of diuretics. Adverse reactions during converting enzyme inhibitor treatment in the elderly may be slightly more frequent than in younger patients, but whether this is related to the drugs themselves or to the general characteristics of elderly hypertensives has not been established. Likewise, whether or not the hypotensive action of converting enzyme inhibitors is age-related is as yet unknown. Finally, studies on the impact of converting enzyme inhibitors on morbidity, mortality and general well being in elderly patients have not been carried out or published. Thus, while the drugs appear to have usefulness in the older hypertensive, their benefits and precise use in this age group are not as yet definitive.
Aged↗
Erythrocyte concentrations and transmembrane fluxes of sodium and potassium in essential hypertension: role of intrinsic and environmental factors.
The intraerythrocyte sodium concentration is increased in the erythrocytes of Zaïrean Bantu with untreated hypertension, while the red blood cell potassium is not different from that of normotensive subjects. Compared with whites, normotensive healthy blacks have a higher intracellular concentration of sodium due to a depressed activity of the sodium-potassium pump. Normotensive healthy males with a positive familial background of hypertension display higher erythrocyte sodium and lower cotransport activity. None of the two measurements offer a clear-cut genetic marker of essential hypertension. In healthy women, the erythrocyte sodium concentration is lowered during the luteal as compared with the follicular phase of the menstrual cycle. This variability explains the difference observed between men and women. A low-sodium diet stimulates the activity of the sodium-potassium ATPase pump, which leads to a decrease in the erythrocyte sodium concentration. Both alterations reverse only slowly during sodium repletion. It is therefore suggested that an adequate matching for race, sex, stage of the menstrual cycle (in women), family history of hypertension, and the amount of sodium in the diet should be a prerequisite for valid conclusions when interpreting the erythrocyte concentration and fluxes of sodium.
Biological Transport, Active↗