![]() Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease.Neyses, Ludwig ; in Journal of Hypertension. Supplement) (1990), 8(4), 99-102 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 153 (1 UL)![]() Impaired relaxation of the hypertrophied myocardium is potentiated by angiotensin II.Neyses, Ludwig ; in Journal of Hypertension. Supplement) (1989), 7(6), 104-5 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 178 (1 UL)![]() High density lipoproteins--modulators of the calcium channel?; Neyses, Ludwig ; et alin Journal of Hypertension. Supplement) (1985), 3(3), 49-51 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 164 (1 UL)![]() Compliance with salt restriction as a limiting factor in the primary prevention of hypertension.Neyses, Ludwig ; ; et alin Journal of Hypertension. Supplement) (1985), 3(1), 87-90 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 202 (1 UL)![]() A simple and effective method to teach patients about high blood pressure and obesity.Neyses, Ludwig ; ; et alin Journal of Hypertension. Supplement) (1985), 3(1), 27-30 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 189 (6 UL)![]() Human red blood cells--an ideal model system for the action of calcium agonists and antagonists.; Neyses, Ludwig ; et alin Journal of Hypertension. Supplement) (1984), 2(3), 577-80 To characterize the pharmacological properties of the slow calcium channel of human red blood cells, we studied the action of various calcium antagonists and two agonists on the 45Ca2+-influx. The Ca2 ... [more ▼] To characterize the pharmacological properties of the slow calcium channel of human red blood cells, we studied the action of various calcium antagonists and two agonists on the 45Ca2+-influx. The Ca2+-ejecting ATPase was inhibited by vanadate. All dihydropyridine derivatives tested showed their inhibiting or stimulating effect on the channel at concentrations attainable in vivo (nitrendipine:Ki = 2.5; Bayer K 6244:Ki 5 microM; nicardipine:Ki = 15 microM, Ks = 0.5 microM; Ciba 28 392:Ki = 20, Ks = 0.3 microM; Ki = inhibition constant, Ks = stimulation constant). Of special interest was the biphasic behaviour (stimulation and inhibition) of the calcium antagonist nicardipine and the agonist Ciba 28 392. The maximum inhibition by the phenylalkylamine derivative verapamil was obtained at much higher concentrations (250 microM; Ki = 100). These data suggest that the calcium channel of human red blood cells has pharmacological properties very similar to the channel in heart and smooth muscle cells with respect to dihydropyridine action. Therefore, human red blood cells are an ideal model to study the action of calcium agonists and antagonists. [less ▲] Detailed reference viewed: 189 (1 UL)![]() Cholesterol and its oxidized derivatives modulate the calcium channel in human red blood cells.Neyses, Ludwig ; ; et alin Journal of Hypertension. Supplement) (1984), 2(3), 489-92 The human red blood cell was used as a model system in order to study the effect of cholesterol and its medically important oxidized derivatives (OSC = oxidized sterol compounds) on the calcium entry ... [more ▼] The human red blood cell was used as a model system in order to study the effect of cholesterol and its medically important oxidized derivatives (OSC = oxidized sterol compounds) on the calcium entry channel. The calcium-ejecting adenosine triphosphatase (ATPase) was inhibited by vanadate and the influx of 45Ca2-into the cells measured. The cells were loaded with OSC at concentrations between 0.075 and 1.5 micrograms OSC/10(7) cells. Two classes of OSC could be distinguished: one stimulating Ca2+ influx dose-dependently by almost 100% at maximum concentrations, the other inhibiting it dose-dependently by up to 80%. The calcium channel blocker nitrendipine inhibited influx by 70% at 15 microM. More than 90% of the total stimulation or inhibition was accounted for by an influence on the nitrendipine-inhibitable part of influx, i.e. the calcium channel. Cholesterol (incorporated using liposomes) had a stimulatory (+288%), cholesterol depletion an inhibitory effect on calcium influx (-18%). These results demonstrate that cholesterol and its oxidized derivatives modulate the calcium channel in a highly stereospecific manner and provide new insights into the mechanism of action and the atherogenic effect of these compounds. [less ▲] Detailed reference viewed: 161 (1 UL) |
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