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L Neyses

Publications and source records attributed to L Neyses.

At least 55 records · Page 3Linked to original sources
PubMed1990

Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease.

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease.

Angiotensin II↗
PubMed1989

Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes.

Isolated calcium-tolerant rat ventricular cardiomyocytes were used to characterize the effects of atrial natriuretic peptide (ANP), Angiotensin II (AII) and their interaction on the myocardial contraction-/relaxation pattern free of interference from other types of cardiac cells. Binding of 125I-ANP showed a KD of 12 pM and approximately 600 binding sites per cell. At 37 degrees C (rate 140 bpm) ANP decreased the contraction maximum with an EC50 of about 70 pM, maximal decrease was 35%. ANP (10(-7) M) raised cellular cyclic-GMP from 0.76+/-0.12 to 1.32+/-0.13 pmole/10(6) cells (73%, p less than 0.05). Angiotensin II increased contractility by a maximum of 32% at 10(-7) M; the EC50 was 8 x 10(-10) M. AII markedly delayed relaxation (reduction of maximum relaxation velocity from 0.092 to 0.063 mm/s; p less than 0.05). ANP (10(-7) M) increased the effect of AII (10(-8) M) on contractility by 66% without changing relaxation parameters significantly. This unexpected interaction may be relevant in pathological conditions where both AII and ANP are stimulated, such as heart failure or secondary hypertension.

Angiotensin II↗
PubMed1989

[Increased atrial natriuretic peptide in essential hypertension--relation to right atrial pressure behavior].

The role of atrial natriuretic peptide (ANP) in the pathogenesis of essential hypertension has not yet entirely been clarified. We investigated whether the increase of ANP in essential hypertension may be explained by elevated right atrial pressures and/or a different relationship between right atrial pressures and ANP secretion. Patients with stable essential hypertension undergoing right and left heart catheterization because of suspected coronary heart disease had significantly higher ANP levels than normotensives: 58.7 +/- 6.7 pg/ml in hypertensives versus 42.0 +/- 4.1 pg/ml in normotensives (p less than 0.01). Matching hypertensives with normotensives at identical levels of left ventricular enddiastolic pressure revealed significantly higher mean pulmonary artery pressures in hypertensives. Right atrial diastolic pressure (v-wave) after matching for LVEDP was 4.8 +/- 0.5 mm Hg in hypertensives and 3.1 +/- 0.2 mm Hg in normotensives (p less than 0.05). In addition, at any given mean right atrial pressure hypertensives showed higher ANP levels than normotensives. These results demonstrate that hypertensives exhibit raised pressures in the pulmonary artery independent of left ventricular pressure load. The elevation in right atrial pressures and the steeper relationship between these pressures and ANP are a suitable explanation for raised ANP levels in hypertension. ANP in essential hypertension may represent a counterregulation against elevated pulmonary resistance.

Adult↗
PubMed1989

Impaired relaxation of the hypertrophied myocardium is potentiated by angiotensin II.

Relaxation delay is an important feature of hypertensive heart disease which impairs diastolic coronary flow and ventricular filling and therefore contributes to heart failure. We investigated the hypothesis that impaired relaxation is a property of the myocardium, rather than the consequence of ischaemia or interstitial fibrosis. A new videomicroscope system was used to define the contraction-relaxation cycle of isolated cardiac myocytes from spontaneously hypertensive rats (SHR) and normotensive control (Wistar-Kyoto, WKY) rats. The SHR cells showed a marked relaxation delay. Angiotensin II (Ang II) increased the contraction maximum by about 35% in WKY rats and induced a relaxation delay. In SHR Ang II greatly potentiated this relaxation delay. Our results demonstrate that impairment of relaxation is a property of the single cardiomyocyte. Angiotensin II induces a relaxation delay that is independent of blood pressure. The combination of hypertrophy and high levels of Ang II potentiates relaxation impairment and may therefore contribute to hypertensive left ventricular failure.

Angiotensin II↗
PubMed1988

[Diagnostic and prognostic value of plasma ANP determination after myocardial infarction].

In the present study the prognostic value of ANP measurement was investigated in 52 patients undergoing coronary angiography. 22 normotensive and 30 hypertensive subjects were included. A significant inverse correlation between left ventricular ejection fraction (EF) and plasma ANP was found in normotensives, but not in hypertensives. In patients with chronic myocardial infarction, there was no difference in ANP levels compared to patients without infarction in either group, provided that EF was normal. However, hypertensives showed a 35% increase in ANP compared to normotensives. This was true for subjects with and without myocardial infarction. These results show that in normotensives ANP levels have a prognostic value on a statistical rather than an individual basis. This does not apply to hypertensives, whose ANP level is increased by factors other than impaired ejection fraction.

Angiocardiography↗
PubMed1988

[Elevated levels of atrial natriuretic peptide and plasma catecholamines in arterial hypertension--indications for an interaction].

In this study plasma levels of atrial natriuretic peptide and of the catecholamines epinephrine and norepinephrine were investigated in hypertensive patients (HT) (n = 30). 22 normotensive patients (NT) served as controls. Hypertensives showed an elevated ANP-level in comparison with controls (46.8 +/- 3.3 vs. 36.8 +/- 3.3 pg/ml, M +/- SEM, p less than 0.01). When patients with myocardial infarction or with reduced ejection fraction were excluded, the same relation was demonstrated (49.3 +/- 3.2 vs. 33.6 +/- 2.0 pg/ml, p less than 0.01). Plasma norepinephrine was 230.8 +/- 52.3 pg/ml in HT compared with 138.0 +/- 19.6 pg/ml in NT (p less than 0.05). Epinephrine was 70.8 +/- 10.5 vs. 54.8 +/- 9.7 pg/ml in HT and NT. To exclude an increased left ventricular enddiastolic - and hence left atrial - pressure as the cause for the elevation of ANP and norepinephrine, HT and NT were matched for the same levels of enddiastolic pressure (LVEDP) (n = 18). For each level of LVEDP ANP was higher in HT than in NT (p less than 0.01). The same held true for norepinephrine (p less than 0.05) and to a lesser extent for epinephrine (p = 0.09). Our results demonstrate that patients with essential hypertension exhibit markedly elevated levels for ANP and catecholamines which is not due to myocardial failure. We propose that the increased secretion of the vasodilatory hormone ANP serves as counterregulation against the vasoconstrictor norepinephrine. The endocrine function of the heart may play a pivotal role in the modulation of sympathetic activity.

Aged↗
PubMed1988

[Concentrations of amiodarone and flecainide in plasma and saliva--indications for the active transport of flecainide].

UNLABELLED: Only the free protein-unbound drug concentration in plasma is pharmacologically active. The concentration of some drugs in saliva is equal to the free drug level. We compared concentrations (in plasma before, 30 and 60 min after the morning dose, in saliva before, 30, 60, 90 and 120 min after the morning dose) of amiodarone (n = 8, 2 x 200 mg orally per day) and flecainide (n = 16, 2 x 100 mg) administered as chronic antiarrhythmic treatment. Drug levels were measured by "high performance liquid chromatography". RESULTS: Just prior to the first morning dose, amiodarone concentrations in plasma were 1.0-2.9 (2.0 +/- 0.6) micrograms/ml, in saliva 0.02-0.25 micrograms/ml; flecainide in plasma 80-560 (316 +/- 163) ng/ml, in saliva 630-3700 (1749 +/- 963) ng/ml. After the morning dose we found maximal flecainide plasma levels of 462 +/- 203 and saliva levels of 3218 +/- 2857 ng/ml. The highest flecainide concentrations in the saliva (13,400 and 11,300 ng/ml) were found in two patients 30 and 60 min after the morning dose. Flecainide, but not amiodarone, is excreted actively in the saliva, probably indicating an enteroenteric circulation. This should be considered to reduce life-threatening flecainide intoxications by gastric and intestinal lavage and suction. The concentration of flecainide in the saliva does not represent the non-protein-bound free drug level in the plasma.

Adult↗
PubMed1987

[Elevated plasma flecainide concentrations in heart failure].

In 42 patients with heart failure who were on long-term treatment with flecainide (2 X 100 mg daily by mouth) plasma concentration of flecainide was measured before the morning dose and compared with the clinical grade of heart failure or left ventricular ejection fraction (in the levo-angiogram). Mean plasma flecainide concentration was 415 +/- 244 ng/ml (110-1035 ng/ml), mean ejection fraction 55 +/- 17.7% (24-84%) (r = -0.60). In seven patients with plasma concentrations over 700 ng/ml (870 +/- 150 ng/ml) in clinical grade III or IV, ejection fractions were 24, 25, 25, 30, 33, 37 and 44%, respectively. In two patients (ejection fraction of 24 and 25%, respectively) the morning plasma concentration was around 1000 ng/ml. The results point to possible high plasma flecainide concentrations--at times in the toxic range--in patients who are in heart failure. In patients with marked reduction in left ventricular pumping function who are on long-term flecainide treatment, a reduction in dosage or monitoring of plasma flecainide concentration is indicated.

Adult↗
PubMed1985

Phosphorylation of the Ca2+-pumping ATPase of heart sarcolemma and erythrocyte plasma membrane by the cAMP-dependent protein kinase.

The Ca2+ ATPase of heart sarcolemma was stimulated by the exposure of sarcolemma vesicles to ATP and the catalytic subunit of the cAMP-dependent protein kinase. The effect of the phosphorylation system was primarily on the Km(Ca2+) of the pumping ATPase. The ATPase purified from heart sarcolemma or erythrocytes became phosphorylated under the conditions mentioned above. Hydroxylamine treatment of the labeled ATPase has shown that the phosphorylation was additive to be acylphosphate formed on the ATPase during the reaction cycle. The stoichiometry of the kinase-promoted phosphorylation (i.e. the fraction of the ATPase molecules that became labeled) approached 30% with both the heart and the erythrocyte enzyme.

Animals↗
PubMed1985

Stereospecific modulation of the calcium channel in human erythrocytes by cholesterol and its oxidized derivatives.

To study the effect of cholesterol and its pathophysiologically important oxidized derivatives (OSC) on the calcium entry channel, the human red blood cell was used as a model system. The calcium ejecting adenosinetriphosphatase (ATPase) was inhibited by vanadate. The cells were loaded with OSC at concentrations between 1.25 X 10(-5) and 25 X 10(-5) mol/l. 22-Hydroxycholesterol, cholestan-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol,3 beta,5 alpha-dihydroxycholestan-6-one and 3 beta-hydroxy-5 alpha-cholestan-7-one stimulated 45Ca2+ influx by up to almost 90%, whereas 25-hydroxycholesterol, 7 beta-hydroxycholesterol, 20 alpha-hydroxycholesterol and 7-oxocholesterol inhibited influx by up to 75%. Both stimulation and inhibition were dependent on the amount of OSC incorporated into the membrane. More than 90% of the total modification of calcium influx by OSC was accounted for by an influence on the nitrendipine-inhibitable part of influx. Enrichment of cholesterol in the membrane greatly stimulated, and cholesterol depletion inhibited, Ca2+ influx. These results demonstrate that cholesterol and its oxidized derivatives are able to modulate the calcium channel in human red blood cells in a highly stereospecific manner.

Calcium↗
PubMed1985

A simple and effective method to teach patients about high blood pressure and obesity.

It is an open question whether information about hypertension and obesity increases compliance with therapy. Nevertheless, patients increasingly demand precise but simple and comprehensive information. A simple slide programme is described which can be demonstrated in any waiting room. The learning effect was assessed in 1083 subjects, of whom 485 had seen the programme completely; 256 subjects served as controls. The percentage of subjects with good or excellent knowledge about hypertension and obesity rose from 22.8% in the controls to 64.2% in the experimental group. Age was the only factor influencing learning, but this was of no great importance in subjects under 70. In particular, social status did not have any significant effect on learning. This programme may be an ideal tool to inform patients about hypertension and obesity and to study the influence of information on compliance with therapy.

Age Factors↗
PubMed1985

High density lipoproteins--modulators of the calcium channel?

It has recently been shown that human red blood cells possess a voltage-independent calcium channel which can be influenced by in vitro modification of the membraneous cholesterol content. To determine whether there is also a link between plasma lipids and the calcium influx through this channel under in vivo conditions, the calcium influx was measured in red blood cells from 51 male donors (aged 41 +/- 5 years). The influx through the channel was defined as the nitrendipine (15 mumol/l)-inhibitable part of 45Ca2+ influx. The Ca(2+)-ejecting ATPase was inhibited by vanadate. The results demonstrate a strong inverse relationship (r = -0.81; P < 0.001) between the plasma concentration of high density lipoproteins (HDL) and 45Ca2+ influx. No significant correlation was found between 45Ca2+ influx and triglycerides, low density lipoproteins (LDL), very low density lipoproteins (VLDL), total plasma cholesterol or extracellular electrolytes (K+, Na+, Ca2+, Mg2+). The results indicate that HDL are involved in the modulation of the calcium channel and provide a link between the cellular cholesterol turnover and the calcium influx in the pathogenesis of atherosclerosis and hypertension.

Adult↗
PubMed1985

Compliance with salt restriction as a limiting factor in the primary prevention of hypertension.

It is an important but still unresolved question whether reduction of salt intake in the offspring of hypertensives (a high risk group) prevents the development of the disease. Therefore, 178 offspring (14-26 years old) of hypertensives were enrolled in a 2-year pilot trial aimed mainly at a reduction in salt consumption. For the intervention group (n = 99) a behavioural approach was chosen with extensive counselling by experienced dietitians. The controls (n = 79) received no continuous dietary advice. Both groups showed a small decline in sodium intake over time, but the differences between the two groups were not significant. Division into subgroups with and without sodium reduction revealed no differences in blood pressure. We conclude that the inherent resistance to any change of lifestyle among healthy subjects may require new and more comprehensive motivational approaches.

Adolescent↗
PubMed1984

The cholesterol content of the human erythrocyte influences calcium influx through the channel.

In order to study the influence of the cholesterol content on the calcium entry channel, the human red blood cell was used as a model system. The cholesterol to lecithin ratio (C/L ratio) of the membrane was modified experimentally by incubating the cells (15h, 25 degrees) with liposomes of defined C/L ratios. Subsequently, net 45Calcium-influx into the cell was measured by inhibiting the Ca-ejecting ATPase with vanadate. Additionally, the use of nitrendipine, a potent calcium channel inhibitor, during incubation allowed the determination of Ca-influx through the calcium channel. A positive correlation between the 45Ca++-influx and the molar C/L ratio of the membrane was found over a wide C/L range. A molar C/L ratio of 1.4 in the membrane increased calcium influx by 150 % compared to controls (molar C/L ratio = 0.8, calcium influx rate = 100 %), while a molar C/L ratio at less than 0.75 decreased calcium influx by 50 %. We conclude, that the cholesterol content of the membrane greatly influences the calcium channel and thus plays a pivotal role for the availability of calcium as a second messenger. These findings may provide a link between high plasma cholesterol and the development of atherosclerosis as well as enhanced platelet aggregability.

Calcium↗