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Biomedical subjects

B Weisser

Publications and source records attributed to B Weisser.

At least 55 records · Page 3Linked to original sources

Low density lipoprotein subfractions and [Ca2+]i in vascular smooth muscle cells.

Several studies have established that plasma low density lipoprotein (LDL) consists of various discrete subfractions. Using a variety of techniques (analytical ultracentrifugation, equilibrium density gradient ultracentrifugation, and gradient gel electrophoresis), LDL has been fractionated into a maximum of seven subclasses that differ in particle size, density, and physiochemical composition. Recently, a predominance of smaller denser LDL particles has been associated with an increased risk of coronary artery disease. However, other lipoprotein changes, such as elevated triglycerides and lower HDL cholesterol levels, have been shown in patients with a predominance of the smaller denser LDL subfractions. Thus, it is unclear whether the enhanced atherogenic potential is induced by the LDL subfraction pattern per se or by concomitant lipoprotein changes. Because intracellular free Ca2+ is an important second messenger involved in atherogenesis and regulation of vascular tone, we studied the influence of three LDL subfractions (very light [LDL1], 1.030 to 1.033 g/mL; light [LDL2], 1.033 to 1.040 g/mL; and dense [LDL3], 1.040 to 1.045 g/mL) on [Ca2+]i in vascular smooth muscle cells (VSMCs) cultured from rat aorta. LDL subfractions were isolated by density gradient ultracentrifugation from human EDTA-plasma (n = 15). [Ca2+]i was measured by fura 2 fluorescence. Basal [Ca2+]i was 77 +/- 6 nmol/L. Stimulation of VSMCs with dense LDL3 caused a significantly (P < .05) more pronounced increase (+71 +/- 13 nmol/L) compared with LDL1 (+38 +/- 8 nmol/L) and LDL2 (+36 +/- 9 nmol/L). To further investigate the mechanisms leading to the stimulation of [Ca2+]i by LDL subfractions, we incubated VSMCs with the Ca2+ antagonists nifedipine, diltiazem, and verapamil in concentrations up to 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acceptance of 24-hour blood pressure determination].

In interviews with 247 patients acceptance and behaviour during 24-hour-ambulatory blood-pressure recording were studied. In contrast to previous assumptions it was shown that the blood-pressure profile was not recorded during normal activities for a great part of patients. Very often the patients reduced their activity over the day. Our results show that for wider distribution and applications of this procedure the measuring devices have to be improved. A substantial part of patients experienced the ambulatory blood-pressure recording as an comfortable, such that one of eight patients declined a further recording and 20% of the patients complained about disturbed sleep.

Activities of Daily Living↗

Lysolecithin actions on vascular smooth muscle cells.

Oxidation of low density lipoprotein increases its atherogenic potential. During oxidation there is an extensive conversion of lecithin to lysolecithin. In rat aortic smooth muscle cells, 2-25 micrograms/ml lysolecithin elevated cytosolic calcium concentration up to 560%. Lysolecithin (10-20 micrograms/ml) increased [3H]thymidine incorporation from 15 cpm/mg cell protein (controls) up to 189 cpm/mg cell protein. Lysolecithin (10 micrograms/ml) potentiated the PDGF-induced (50 ng/ml) [3H]thymidine incorporation up to 6.3 times. The results indicate that lysolecithin could induce mechanisms, by which oxidized low density lipoproteins could promote cell growth and thus contribute to atherosclerosis.

Animals↗

[Blood pressure measurement using the fingers].

An increasing number of devices for self-assessment of blood pressure has been developed over the past years. Accepted international standards for evaluation of such devices are still lacking. A new apparatus (T88, Marshall Electronics) measuring blood pressure on digital arteries by oscillometry was tested for accuracy. Comparative measurements in 36 patients indicated position-dependent results with a reasonable correlation with the measurements taken on the upper arm only if the device was used at the level of the heart. Significant differences for systolic values were noted on different phalanges. In a last series of measurements, comparing values obtained about the basal phalanges of the index positioned at the level of the heart, significant differences were found for systolic and diastolic values compared to the traditional measurement. The use of this device for evaluation of hypertension, monitoring of treatment or use in studies is thus not recommended.

Arteries↗

[Self measurement of blood pressure: normal and pathological values].

To date, the normal range for self-recorded blood-pressure values has yet to be defined. In this paper possible definitions of the normal range of self-recorded blood pressure are discussed. In large epidemiologic studies self-recorded and casual blood-pressure values should be compared to each other, and in prospective interventional studies blood-pressure values for the initiation of therapy should be defined. Before the termination of these studies we recommend the start of an antihypertensive therapy above 140/90 mmHg. Although definite normal values for self-recorded blood pressure are still missing, a broader use of this method seems to be justified because of the well-known pitfalls of the causal clinical blood-pressure measurement.

Blood Pressure Determination↗

[Are mercury sphygmomanometers obsolete?].

The measurement of blood pressure during medical visits is limited in its diagnostic, prognostic and therapeutic value by physiologic variability of hypertension and measurement errors. Repeated measurements reduce the effect of spontaneous variations of blood pressure. They allow a more secure assessment of real tension. Regular training for proper technique and elimination of arbitrary preference for rounded last digits or automated recording minimize erroneous measurements. By the multitude of recorded parameters the ambulatory measurement over 24 hours and the self-assessment of blood pressure provide a representative diurnal profile superior to individual measurements at the doctors office. Each of the two methods has its own field of application, although prognostic and therapeutic aims seem similar. The continuous recording over 24 hours is suited for initial assessment and identification of hypertensive patients. Self-assessment of blood pressure has its use for long-term follow up and optimization of therapy. Both methods are complementary and only limited from wider use by lacking internationally accepted normal values and standardization of available devices.

Blood Pressure↗

[Combination therapy of cardiovascular risk factors].

Risk factors for cardiovascular diseases, which are the leading cause of mortality in the industrialized countries, are well investigated; however, the results of intervention studies on the therapy of single risk factors were disappointing in the past. Recently, there has been growing evidence that there might be a closer pathophysiological relation between arterial hypertension, hypercholesterolemia, obesity, impaired glucose tolerance and genetic disposition than previously thought. For the treatment of the individual patient, this concept requires a complete work-up and comprehensive therapy of all risk factors. The therapy of several mildly elevated risk factors may be more beneficial than a too vigorous reduction of the blood pressure alone. At the beginning of every therapeutic regimen, there has to be a nonpharmacological approach. Diet and weight reduction even in mild obesity are more efficient in influencing several risk factors at the same time than pharmacological therapy. Metabolic consequences of drug treatment have to be carefully monitored.

Cardiovascular Diseases↗

Comparison of casual, ambulatory and self-measured blood pressure in a study of nitrendipine vs bisoprolol.

In a double-blind, placebo-controlled study the antihypertensive efficacy and tolerability of a single morning dose of either 10 mg bisoprolol (n = 26) or 20 mg nitrendipine (n = 27) were investigated. Blood pressure was measured by three techniques: (1) Casual blood pressure 24 h after the dose; (2) ambulatory 24-h whole-day monitoring; and (3) self-recorded blood pressure in the morning 24 h after the dose (6-8 a.m.) and in the evening (6-8 p.m.). After 4 weeks of therapy bisoprolol had produced a highly significant reduction in blood pressure as assessed by causal, ambulatory day- and night-time monitoring, and self-measured morning and evening readings. Bisoprolol was significantly more effective than nitrendipine, which did not induce a significant reduction in the ambulatory night-time recordings. Whole-day ambulatory blood pressure profiles showed an antihypertensive effect of bisoprolol throughout the entire 24-h period. 24-h blood pressure curves after nitrendipine demonstrated a markedly shorter duration of action, with no reduction in early morning blood pressure. Adverse effects and tolerability of the two drugs were comparable. The average changes in systolic and diastolic blood pressure after bisoprolol and nitrendipine in 2-h periods of ambulatory monitoring (6-8 a.m. and 6-8 p.m.) and self-measured blood pressure (6-8 a.m. and 6-8 p.m.) showed a good agreement between ambulatory and self-measured blood pressure determinations with no significant difference between the methods. The results show that 24 h antihypertensive efficacy was more pronounced for bisoprolol than for nitrendipine at the doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Inhibition of cyclooxygenase attenuates baroreceptor function and increases the pressor response to norepinephrine in man.

The possible influence of prostaglandins on baroreceptor function in man has been investigated. Baroreceptor reflex was activated by intravenous infusion of norepinephrine and the pressor response was measured, both before and after administration of indomethacin. Resting blood pressure remained unchanged after indomethacin while resting heart rate was significantly decreased as compared to placebo and the norepinephrine-induced rise in mean arterial blood pressure was significantly more pronounced. The baroreceptor-mediated decrease in heart rate tended to be smaller. Baroreceptor sensitivity (delta heart rate/delta blood pressure) was significantly reduced by indomethacin to about half of the control value. In addition to attenuation of sensitivity, the findings represent resetting of the baroreceptor setpoint and a more pronounced pressor response to norepinephrine after cyclooxygenase inhibition. Thus, eicosanoids originating via the cyclooxygenase pathway of arachidonate metabolism may modulate the vascular response to adrenergic stimulation and may participate in the regulation of baroreceptor reflex setpoint and sensitivity.

Adult↗

An evaluation of self-measured blood pressure in a study with a calcium-channel antagonist versus a beta-blocker.

In recent years self-measurement of blood pressure at home has gained increasing importance but there have been only a few studies comparing casual, ambulatory, and self-measured blood pressure determinations during a single clinical trial. We therefore compared treatment-induced blood pressure-reductions in a double-blind, placebo-controlled, parallel study design with a single morning dose of either 10 mg bisoprolol (n = 26) or 20 mg nitrendipine (n = 27) with casual blood pressure readings in the morning before the dose, ambulatory 24-h monitoring, and self-recorded measurements in the morning before the dose and in the evening. Mean reductions for systolic and diastolic blood pressure after 4 weeks of therapy were significantly greater for bisoprolol than for nitrendipine. The treatment-induced blood pressure reductions were most pronounced as assessed by casual readings but showed good agreement between casual, ambulatory, and self-measured blood pressure for group comparisons. In some patients, however, marked individual differences between the three methods were observed. Correlation coefficients between ambulatory and self-measured blood pressure were 0.4 for systolic blood pressure (P less than .05) and 0.6 for diastolic blood pressure (P less than .0005). Under the conditions of this parallel study design and the usual statistical risks, a difference of 5 mm Hg in diastolic blood pressure can be detected in 118 patients at the clinic, in 70 patients if ambulatory blood pressure is used, or in 56 patients if self-measured blood pressure is used. In conclusion, bisoprolol was more effective over 24 h than nitrendipine at the doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Long-term diuretic therapy: effects of dose reduction on antihypertensive efficacy and counterregulatory systems.

In the present study, the effects of a dose reduction on antihypertensive efficacy and metabolic side effects of diuretic therapy were investigated in 36 hypertensive patients. During the first treatment period of 1 year, the patients were treated with 25 mg of the thiazide diuretic bemetizide (n = 18) or 25 mg bemetizide plus 50 mg of the potassium-sparing agent triamterene (n = 18). Mean blood pressure (BP) values decreased significantly (p less than 0.01) during the first year of the trial. Thereafter, doses were reduced to 10 mg bemetizide or 10 mg bemetizide plus 20 mg triamterene in patients whose BP became normal during the first year (n = 16 in both groups). At the end of the second year, equal BP control was achieved with doses more than twice smaller than those used during the first year. During the second year of the trial, activation of the renin-angiotensin system (RAS) was significantly less pronounced as compared with the first year and the percentage of patients with hypokalemia (less than 3.5 mM) decreased from 62.5 to 25% in the bemetizide group. Thus, this long-term study provides additional evidence that diuretics have a flat dose-response curve with respect to their antihypertensive efficacy, whereas lower doses might cause less pronounced activation of counter-regulatory systems. Furthermore, our results indicate that long-term studies might be necessary to assess the full antihypertensive potential of low doses of antihypertensive agents.

Aldosterone↗

Oxidized low-density lipoproteins in atherogenesis: possible mechanisms of action.

The increased atherogenic potential of oxidized low-density lipoprotein (ox-LDL) is well documented. In the present study, we investigated possible mechanisms of action of the difference to native LDL. In vitro oxidation of LDL was determined by measurement of thiobarbituric acid-reacting substances and absorption at 234 nm. Copper (5 mumol/L) induced significant (p less than 0.01) oxidation in vitro. Furthermore, LDL isolated from atherosclerotic patients was slightly but significantly (p less than 0.05) more oxidized than LDL from normal controls (2.81 +/- 0.08 vs. 3.21 +/- 0.16 nmol of TBARS/mg of LDL protein). Ox-LDL caused significantly (p less than 0.01) more pronounced contractions of rat aortic rings in vitro compared to nonoxidized LDL expressed as a percentage of maximal contractions induced by 40 mmol/L of KCl (29.0 +/- 5.4% vs. 61.1 +/- 7.2%). Lysolecithin, which is a principal component of ox-LDL formed during oxidation, induced a dose-dependent increase in intracellular free calcium in vascular smooth muscle cells cultured from rat aorta. Doses from 2-25 micrograms/ml were tested and caused a maximum increase of more than 500% (25 micrograms/ml). In conclusion, this study provides further evidence for a higher biological activity of ox-LDL. Lysolecithin might be one of the active components formed during oxidation of LDL.

Animals↗

Oxidation of low density lipoprotein enhances its potential to increase intracellular free calcium concentration in vascular smooth muscle cells.

There have been suggestions that oxidation of low density lipoproteins (LDL) might increase their atherogenic potential. Because changes in intracellular free calcium concentration [Ca2+]i have been linked to atherogenesis, we compared the influence of oxidized LDL (Ox-LDL) and native LDL (N-LDL) on [Ca2+]i in vascular smooth muscle cells cultured from rat aortas. For determination of [Ca2+]i, fura-2 fluorescence was used. LDL was isolated by ultracentrifugation from the sera of human donors (n = 17). In N-LDL, oxidation was prevented by addition of antioxidants, whereas Ox-LDL was obtained by auto-oxidation. The extent of oxidation was assessed by measurement of thiobarbituric acid-reactive substances. Addition of Ox-LDL (20 micrograms protein/ml) to the vascular smooth muscle cells induced a mean increase of 129 +/- 13% in [Ca2+]i compared with 81 +/- 7% with N-LDL (p less than 0.01). Dose-response curves from 1 to 20 micrograms/ml (six experiments) confirmed this difference within the entire dose range. These results indicate that a more pronounced increase in [Ca2+]i induced by Ox-LDL might be one of the cellular mechanisms responsible for the higher atherogenic potential of Ox-LDL compared with N-LDL, as [Ca2+]i is an important second-messenger system involved in many atherogenic processes such as hypertrophy, cell migration, and cell damage.

Animals↗

Betablocking drugs in essential hypertension: transdermal bupranolol compared with oral metoprolol.

In the present study the antihypertensive efficacy and tolerability of transdermal bupranolol (30 mg once-daily) was compared with oral metoprolol (100 mg once-daily). Blood pressure measurements were performed in the office, at home, and with ambulatory 24-h blood pressure devices. Systemic and local side-effects, as well as compliance and acceptance, were evaluated every two weeks. The treatment period lasted eight weeks. The results showed a significant decrease in blood pressure under the bupranolol transdermal therapeutic system in the office, at home, and with 24-h blood pressure measurements day- (08h00-20h00) and night-time (20h00-08h00). Under oral metoprolol there was a significant blood pressure decrease in the office, at home, and in the mean daytime values of the 24-h blood pressure measurements. The night-time values, however, demonstrated only a slight decrease in blood pressure, being significant only for diastolic values. Systemic side-effects were comparable in both groups. 69% of the patients had local side-effects at the patch side (erythema, papulous exanthema, pruritus). Six patients dropped out because of localized urticarial exanthema (five patients treated with transdermal bupranolol, one patient treated with oral metoprolol). In comparison to the oral form, twice as many patients had admitted to have been non-compliant with the patches (13 versus 7 patients). At the end of the study, 24 out of 32 patients preferred to be treated with capsules.

Administration, Cutaneous↗