Biomedical subjects

U Decking

Publications and source records attributed to U Decking.

4 recordsLinked to original sources

PubMed2000

Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of spontaneously hypertensive rats.

Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy metabolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontaneously hypertensive rats (SHR) is associated with an impaired myocardial energy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60, and 80 weeks, respectively (each n = 4-5), were perfused according to the working heart technique. Cardiac work and coronary flow were monitored online. Myocardial energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which were measured by nuclear magnetic resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30min at baseline conditions (low afterload), followed by another 30min under a moderate pressure load (high afterload). Each SHR group showed a higher heart weight/body weight ratio than the age-matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1+/-0.3, 60 weeks = 4.0+/-0.3, 80 weeks = 3.8+/-0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82+/-0.06, 60 weeks = 1.69+/-0.05, 80 weeks = 1.59+/-0.09 (PCr/ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capacity of hearts of SHR progressively decreases with increasing age and left ventricular hypertrophy. This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio, suggesting a decreased energy reserve.

Adenosine Triphosphate↗

PubMed1996

Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats.

Adenosine is an inhibitory modulator in the mammalian brain with a possible role in sleep regulation, which is mainly indicated by pharmacological studies showing that adenosine or its analogs can induce sedation and sleep, whereas adenosine antagonists, like caffeine and theophylline, are potent behavioral and neuronal stimulants. In contrast to these pharmacological findings, data on endogenous adenosine in relation to sleep and waking are sparse. Therefore, we have now used in vivo microdialysis to investigate the extracellular levels of adenosine in the neostriatum and hippocampus of freely moving rats. Adenosine was monitored over a time course of 24 h, during which the animals were exposed to a 12 h day/night rhythm with lights-off from 19.00 to 07.00. In this lights-off period, i.e. the rats' active period, the maximal levels of neostriatal and hippocampal extracellular adenosine were higher than during the lights-on period. In contrast to the neostriatum, extracellular levels of hippocampal adenosine tended to increase towards the end of the lights-off period, reaching its maximal level at 07.00, and decreasing again within the following hour. The changes of hippocampal adenosine levels were related to behavior, since significant increases in "sleep-like" behavior, as well as decreases in overall movements and consummatory behavior, were observed when adenosine levels had reached their maxima in the hippocampus; no such relationship was found with respect to the neostriatum. These results are in keeping with a role of endogenous adenosine in the regulation of sleep and wakefulness, and point to a specific role of adenosine in the hippocampus. They also raise the possibility that adenosine may be involved in different behavioral processes dependent on the area of the brain, as well as the type of adenosine receptor involved. Finally, given the known evidence for neuroprotective actions of adenosine, its accumulation in the hippocampus as a function of behavioral activity may serve to prevent or repair the neural degenerative consequences of such activity. It is proposed that adenosine's sleep-promoting effects result from its signalling to cease behavioral activity in order to prevent excessive activity-related changes, and thus allow other restorative sleep-related processes to take over.

Adenosine↗

PubMed1996

[Regulation of coronary circulation by adenosine].

The close coupling between energy expenditure and coronary blood flow has led very early on to the hypothesis, that metabolic factors form the essential link between metabolism and flow. Adenosine has been postulated to be an important mediator since this nucleoside is derived from ATP, readily can permeate through cell membranes and constitutes a potent vasodilator. Several animal studies, mainly performed in the 70ies, demonstrate a close correlation between coronary blood flow and adenosine without proving a causal relationship. More recent studies have concentrated on the cellular and molecular conditions which can be expected to cause an enhanced formation of adenosine. These studies revealed: 1. The free concentration of cytosolic ADP, as measured by NMR-spectroscopy, and the formation and release of adenosine do not measurably increase with elevated workload as long as the oxygen supply is adequate. The relation between free AMP and adenosine is more complex than previously assumed. There is a metabolic cycle between the two metabolites which functions to potentiate adenosine formation with only minor changes in AMP. 2. The coronary endothelium constitutes an important metabolic barrier for adenosine. It also can form adenosine and can liberate ATP which then act on endothelial A2- and P2-receptors, respectively. The relevance of the interrelationship between ATP-receptors, ecto-adenine-nucleotide-cascade and adenosine-receptors is presently only incompletely understood. In functional terms the data in the literature suggest that adenosine is not important for the setting of basal coronary blood flow. Mediators such as NO and endothelin may be more important under these circumstances. Adenosine, however, appears to play an important role under pathophysiological conditions when oxygen supply becomes limiting such as during hypoxia/ischemia, with coronary stenosis and reduced coronary flow reserve.

Adenosine↗

PubMed1994

[Why do endothelial cells require adenosine triphosphate?].

NMR-spectroscopy (31P-NMR, 23Na-NMR) has been used to characterize the energy metabolism of cultured endothelial cells of the pig aorta and to determine the energy requirements of the Na-K-ATPase relative to total cellular energy consumption. Endothelial cells exhibited high concentrations of creatine phosphate and cardiac microvascular creatine kinase (CK) was of the BB-CK subtype. BB-CK can therefore be used as a marker-enzyme of endothelial cells in muscular organs. The transmembrane flux-rate of sodium was 117 mumol Nalmin/mg prot in the steady state at an intracellular sodium concentration of 25 mmol/l. Combining microcalorimetric measurements with 23Na-NMR data revealed that the energy requirement of endothelial Na-K-ATPase despite the high surface to volume ratio comprises only 3-5% of total cellular energy consumption.

Adenosine Triphosphate↗