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J Aussedat

Publications and source records attributed to J Aussedat.

At least 37 records · Page 2Linked to original sources
PubMed1985

[Absence, in the hypertrophied rat heart caused by aortocaval fistula, of several metabolic and electrophysiological changes seen in other models of hypertrophy].

In this work, we compared the electrophysiological and metabolic parameters of a volume overload model of cardiac hypertrophy (aorto-caval fistula) with those of two other models of hypertrophy (aortic stenosis and isoproterenol pretreatment). In these last models, a prolongation of action potential and a decrease of myocardial ATP content are observed. However, these alterations are not shown in the aorto-caval fistulated animals while their heart are well hypertrophied. The amplitude increase of phase 3 AP seemed to be a common factor of these models of cardiac hypertrophy.

Action Potentials↗
PubMed1984

Pyrimidine nucleotide metabolism in cardiac hypertrophy.

Cardiac hypertrophy was induced in rats either by isoprenaline treatment or by experimental abdominal aortic stenosis. In both models, the UTP content increased in the hypertrophying heart, while the ATP level remained depressed. The rate of net synthesis of uracil nucleotides, estimated by phosphate incorporation into alpha-phosphate groups, was largely increased during the first stage of hypertrophy (X 3.6 and 2.6, respectively). At identical stages of hypertrophy, the rate of synthesis of ribosomal RNA, measured after continuous intracardiac infusion of 3H-uridine, was increased by 1.6 and 2.5 times. A comparison of the changes in time course of the levels of UTP and RNA and their turnover suggests that the metabolism of uracil nucleotides and that of ribosomal RNA are closely interrelated. The increase in the rate of synthesis of pyrimidine is interpreted as an adaptational change in nucleotide metabolism in response to the increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.

Adenosine Triphosphate↗
PubMed1984

[Synthesis of adenine nucleotides from exogenous adenosine in the perfused rat heart under normoxic conditions and after ischemia].

The rate of synthesis of myocardial adenine nucleotides from exogenous adenosine was studied in the isolated rat heart perfused under normoxic conditions and following ischaemia. The rate of incorporation of adenosine depended on the extracellular concentration of the precursor, following Michaelis-Menten kinetics with a apparent Km of 51.3 microM and a maximal rate of incorporation of about 1 100 nmol g-1 (wet wt.) 30 min-1. The adenosine uptake induced an increase in ATP concentration (+ 20%) when the exogenous concentration of precursor exceeded 10 microM. Following low-flow ischaemia (0.5 ml/min, 30 min), the rate of incorporation of 5 microM adenosine was diminished (-23%), but adenine nucleotide level restoration was favoured by the nucleoside administration. After total ischaemia (24 min), the extent of the decrease in adenosine incorporation was the same as in the case of moderate ischaemia but adenine nucleotide content was not restored.

Adenine Nucleotides↗
PubMed1984

[Physiopathologic modifications in the myocardial levels of adenine nucleotides].

When the equilibrium between energy production and utilization is disrupted in the myocardium, the metabolism of adenine nucleotides is greatly altered. The first alteration is a change in the degree of phosphorylation which induces alterations in the respective amounts of AMP, ADP and ATP. This change, in turn, creates an imbalance between synthesis and degradation of adenine nucleotides. As a consequence, the levels of AMP, ADP and ATP are not restored when physiological conditions are reestablished. The aim of this paper is to describe the alterations of adenine nucleotides which occur in physiopathological conditions (ischemia, hypertrophy) and to discuss the use of the levels of AMP, ADP and ATP as indicators of the metabolic state of the heart. Brief descriptions of the methods used for determinations of concentrations and of the processes of energy transfer and adenine nucleotide synthesis in the myocardium are given.

Adenine Nucleotides↗
PubMed1984

[Effects of pretreatment with isoprenaline and conditions of perfusion on the specific radioactivity of ATP in rat heart].

14C adenine was supplied to isolated Rat heart retrograde perfused. The experiment was continued by aortic or atrial perfusion and the evolution of the specific radioactivity of ATP was estimated. Aortic perfusion did not reduce ATP content and the specific radioactivity decreased, expressing the turnover of adenine nucleotides. On the contrary, working heart perfusion provoked a breakdown of ATP and an increase of ATP specific radioactivity. When myocardial ATP was decreased prior to the perfusion with isoproterenol, the incorporation of 14C adenine was enhanced, a further aortic perfusion induced a greater decrease of ATP specific activity than in controls. Atrial perfusion did not change the concentration and the specific activity of ATP. These data seem to provide experimental evidences for a compartmentalization of myocardial ATP.

Adenosine Triphosphate↗
PubMed1984

[Acceleration of the synthesis of cardiac adenine nucleotides from adenosine as affected by propranolol].

DL-propranolol, at a dose of 2 mg . l-1, induced in the isolated rat heart an increase in adenine nucleotide synthesis from exogenous 5 microM adenosine (+20%). If supplied during reperfusion following low-flow ischaemia (0.5 ml . min-1, 30 min.), propranolol annulled the decrease in adenosine incorporation (-23%) provoked by ischaemia. When propranolol was given during ischaemia and reperfusion, ATP degradation during the ischaemic period was reduced and adenosine uptake was strongly stimulated on reperfusion (+60%).

Adenine Nucleotides↗
PubMed1983

A method for measuring free-nucleotide pool sizes and incorporation of labeled precursors: its application in studying myocardial pyrimidine nucleotides.

A procedure for a rapid and accurate determination of nucleotide pool sizes in heart muscle is described. The method involves an enzymatic cleavage of all nucleotides by phosphodiesterase to nucleoside 5'-monophosphates and an HPLC separation (Partisil 10 SAX) by isocratic or two-step elution. This method permits reproducible measurements of the pools of pyrimidine nucleotides which are particularly small in cardiac tissue. Moreover, this technique may be conveniently applied in studies on the incorporation of labeled precursors into free nucleotides. Experimental evidence is presented showing the accuracy of the method.

Adenosine Monophosphate↗
PubMed1983

Comparative changes in the 32P labeling of adenine and uracil nucleotides in the hypertrophying rat heart.

The turnover of cardiac adenine and uracil nucleotides was studied in the hypertrophying rat heart by means of the kinetics of incorporation of labeled phosphate into the alpha-phosphate groups of nucleotides. Cardiac hypertrophy was induced either by chronic isoproterenol treatment (5 mg X kg-1 body wt. daily, s.c.) or by abdominal aortic constriction. In both experimental models, although the labeling of alpha-P groups of adenine nucleotides was at first unmodified, the incorporation of [32P]Phosphate into uracil nucleotides was accelerated early and the stimulation maintained for several days. The intramyocardial concentration of UTP and uracil nucleotides rose during the early phase of hypertrophy, while the ATP and adenine nucleotide pools were depleted. All of these alterations were more pronounced in isoproterenol-treated animals than in those with aortic stenosis. In this experimental model (isoproterenol treatment), the hypertrophy develops faster and is accompanied by a larger increase in cardiac RNA concentration. Thus, the increase in the rate of synthesis of uracil nucleotides may be interpreted as an adaptative change of nucleotide metabolism in response to an increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.

Adenine Nucleotides↗
PubMed1983

Effect of uridine supply on glycogen resynthesis after ischaemia in the isolated perfused rat heart.

Isolated rat hearts were subjected to 30 min low flow ischaemia (0.5 ml X min-1). During reperfusion, uridine (5 X 10(-5) mol X litre-1) was added to the perfusion medium for 30 min. The concentrations of creatine phosphate, adenine nucleotides, uridylic nucleotides and glycogen were determined at the end of the experiments. The purpose of this work was to study the effects of uridine supply on the concentration of energetic compounds during reperfusion recovery. Low flow ischaemia induced a breakdown of creatine phosphate, adenosine triphosphate, and total adenine nucleotides by 53%, 23% and 15% respectively. The creatine phosphate content was restored during reperfusion without uridine, but the adenine nucleotides remained unchanged. The uridylic nucleotides and the glycogen were also degraded during ischaemia by 56% and 53% for uridine triphosphate and glycogen respectively. Reperfusion without uridine induced a partial resynthetisation of uridylic nucleotides but glycogen stores were not significantly restored. When tested in oxygenated hearts, uridine supply induced a fall in creatine phosphate concentration and an enhancement of uridine triphosphate level but it had no effect on adenosine triphosphate, uridine diphosphate glucose or glycogen concentrations. If supplied during reperfusion, the nucleoside induced the complete restoration of myocardial ATP, total adenine nucleotide content, an increase in the uridylic nucleotide concentration and the resynthetisation of glycogen to supra-normal value.

Adenine Nucleotides↗
PubMed1981

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats.

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload. Repeated subcutaneous injections of isoproterenol (ISO) (5 mg . kg-1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment. Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated. The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.

Adenine Nucleotides↗
PubMed1980

[Effect of various precursors on the synthesis of adenine and uracil nucleotides in the rat heart (author's transl)].

The dynamics of cardiac adenine and uracil nucleotides, following a subcutaneous injection of isoproterenol, was studied on the rat in vivo. The effect of continuous supply of adenosine, uridine, or ribose on the level of ATP and UTP was investigated on control rats and on isoproterenol-treated animals. The precursors were administered by continuous infusion (1 ml.h-1) into the superior caval vein. 1. ATP and UTP levels were decreased within one hour after a single dose of isoproterenol (5 mg.kg-1) (Fig. 1). 2. Then, the level of ATP rose slowly toward the control value. The normal level was not reached within 48 h (Fig. 1). 3. On the contrary, the initial drop in UTP concentration was followed by a rapid restoration. The control value was reached in 3 h, and then the UTP pool was increased to 180% of the normal level, 12 h after isoproterenol application. 4. As previously shown by other authors, the restoration of ATP was accelerated by a continuous supply of adenosine (37 micromoles per hour) or ribose (170 micromoles per hour) (Fig. 2). 5. The infusion of ribose (170 micromoles per hour) or uridine (41 micromoles per hour) completely suppressed the initial decrease in UTP level caused by beta-receptor stimulation. The further enlargement of the UTP pool was greatly enhanced by ribose or uridine (Fig. 3). 6. The infusion of adenosine was also positive on UTP regeneration. On the contrary, uridine had no effect on the ATP pool (Fig. 3). 7. When supplied to non-treated animals, all precursors caused an enhancement of the UTP level. Adenosine and ribose increased the ATP pool (Fig. 2 and 3). These results contribute to the comparison of the efficiency of the various pathways of cardiac nucleotide synthesis. They show that both de novo synthesis and salvage pathways are limited by the amount of precursors. The increase in UTP synthesis caused by ribose is consistent with the theory put forward for purines (ZIMMER et GERLACH, 1974) that phosphoribosyl-pyrophosphate availability limits the efficiency of de novo synthesis of nucleotides; it demonstrates that this concept is also true for de novo synthesis of pyrimidine nucleotides.

Adenine Nucleotides↗
PubMed1979

[Isoprenaline, modifications of the turnover of ATP in the perfused rat heart].

5 hrs after a single sub-cutaneous injection of the drug in a dose of 5 mg/kg, the ATP concentration was reduced by 15%, the incorporation of 14C adenine was augmented by 20% and the turnover of ATP was accelerated: the reduction of specific radioactivity attained 16%, 75 mn after the period of marquage, instead of 7% in the control hearts. When the drug was added to the perfusion fluid, there was no supplementary reduction of the ATP concentration and the action on the nucleotide turnover only existed if the ATP level was reduced by a pretreatment: the reduction of specific radioactivity then attained 24% after 75 min. of perfusion.

Adenine↗
PubMed1976

[Kinetics of alpha phosphate turnover in the free nucleotides of isolated rabbit hearts during the incorporation of adenosine or uridine].

The isolated rabbit heart was perfused with tritium-labelled adenosine or uridine at constant concentration (respectively 10 and 2 micrometer) and specific activity. The transfer rates of the precursors into free nucleotides were obtained by calculating the uptake of isotope into the products. The rates of phosphorylation of the nucleotides were estimated by following the incorporation of 32PO4 3- into the alpha phosphate groups. The results obtained with the two isotopes show that the rate of labelling of the alpha phosphate groups is a good estimate of the turnover of nucleotides when the mechanism of synthesis involves phosphorylation of a riboside.

Adenine Nucleotides↗
PubMed1976

[Turnover of free adenine nucleotides of the isolated and perfused rabbit heart].

The turnover of free adenine nucleotides was studied in the perfused rabbit heart by the decline in radioactivity 3 h 30 after administration of a single pulse of tritiated adenine. The radioactivity of the perfusate was followed during the experiments. About 7% of the labelled adenine nucleotides were renewed by hour and 1,5% of the radioactivity was lossed by hour in the perfusion fluid.

Adenine Nucleotides↗
PubMedDate not supplied

Pyrimidine nucleotide synthesis from exogenous cytidine in the isolated rat heart.

The rate of incorporation of exogenous cytidine into the pyrimidine nucleotides of isolated perfused rat hearts bears a Michaelis-Menten kinetic relationship to the extracellular concentration of the precursor, with an apparent Km of 10 microM and a maximal rate of incorporation of about 60 nmol per gram (ww) per 30 minutes. The myocardial cytosine nucleotide content was significantly increased by a 30 minute supply of 15 microM cytidine and more than doubled after a 2 hour administration period of 50 microM cytidine. In the latter case, the rate of cytidine incorporation fell by 30% (with respect to the initial uptake) during the last 30 minutes of administration. These results suggest that the uptake of cytidine can play an important part in the myocardial cytosine nucleotide metabolism under physiological conditions.

Animals↗