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A Grynberg

Publications and source records attributed to A Grynberg.

At least 37 records · Page 2Linked to original sources
PubMed1996

Specific effects of n-3 fatty acids and 8-bromo-cGMP on the cyclic nucleotide phosphodiesterase activity in neonatal rat cardiac myocytes.

The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the corresponding isoform present in the heart ventricle of adult rat (70% v 350%). When neonatal rat ventricular myocytes were grown in a medium enriched in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), an increase of the basal level of cAMP and mainly cGMP was observed. The cGMP-PDE specific activity in the unfractionated cytosol of DHA-, EPA- or 8-bromo-cGMP-enriched cardiomyocytes was lower than that observed in control cells. Whereas the cAMP-PDE specific activity remained unchanged whatever the treatment used. At the same time, the response of the cGMP-stimulated PDE to cGMP was substantially increased in n-3 fatty acid-enriched cardiomyocytes and reached the same level as in the whole ventricle (340%). The treatment of neonatal cardiomyocytes with 8-bromo-cGMP also re-established the sensitivity of this cGMP-stimulated isozyme to cGMP (320%). These results suggest a common mechanism for polyunsaturated fatty acids and 8-bromo-cGMP in the regulation of the cGMP-stimulated PDE activity in cardiomyocytes from new-born rats.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Sympathoadrenergic overactivity and lipid metabolism.

Epidemiological studies have identified high heart rates as a risk factor for coronary heart disease mortality, and heart rate was found to correlate with the severity of coronary atherosclerosis. Heart rate was positively correlated with serum concentrations of total cholesterol, triglycerides, and non-HDL cholesterol. Since heart rate responds sensitively to sympathoadrenergic activity, it was hypothesized that catecholamines play a crucial role in the unfavorable lipid alterations. In addition to influences on circulating lipids, the question arose whether catecholamines have more specific effects on molecular species of structural lipids. Of particular importance is the question of the involvement of catecholamines in the recently suggested correlation between arachidonic acid and stroke mortality. It is therefore attempted to delineate the possible effects of catecholamines on the fatty acid composition of the phospholipids of heart muscle and vasculature. This was achieved in rats by either catecholamine injection or by swimming, a condition known to be associated with marked sympatho-adrenergic stimulation. In swimming rats, linoleic acid was decreased by up to 40% in heart phospholipids, whereas stearic acid and arachidonic acid were increased. Similarly, chronic norepinephrine treatment in rats resulted in a net decrease in linoleic acid and an increase in arachidonic acid and docosahexaenoic acid, which was particularly pronounced when rats were fed an n-3 polyunsaturated fatty acid (PUFA)-rich oil diet. Thus, catecholamines do affect the PUFA composition of heart membranes, mainly through an increase in arachidonic acid content. To further define the action of catecholamines on structural lipids, isolated rat ventricular myocytes in culture were subjected four times to 30 minutes of isoproterenol (10(-6) M) stimulation over 48 hours. No changes in membrane lipid parameters were observed, although the beating rate was increased by 30% during the stimulation. When the cell membranes were enriched in n-3 PUFAs (in association with a decrease in arachidonic acid), the positive chronotropic effect elicited by isoproterenol was raised to + 50%, indicating the modulation of adrenergic function by membrane PUFAs. However, isoproterenol treatment again had no effect on the phospholipid fatty acid composition. Thus, the effect of catecholamines on membrane lipids observed in intact organism appears to be indirect and to involve most probably organs such as the liver and adipose tissue. Catecholamines are expected to induce a lipolysis-linked quantitative and qualitative alteration in circulating fatty acids, which in turn alter the heart membrane composition, similar to the composition changes elicited by diet lipid alterations. Since there is increasing evidence that such fatty acid changes affect the activity of membrane proteins, the possibility emerges that this mechanism may contribute to the catecholamine-linked cardiovascular mortality.

Animals↗
PubMed1996

Fatty acid oxidation in the heart.

The heart is known for its ability to produce energy from fatty acids (FA) because of its important beta-oxidation equipment, but it can also derive energy from several other substrates including glucose, pyruvate, and lactate. The cardiac ATP store is limited and can assure only a few seconds of beating. For this reason the cardiac muscle can adapt quickly to the energy demand and may shift from a 100% FA-derived energy production (after a lipid-rich food intake) or any balanced situation (e.g., diabetes, fasting, exercise). These situations are not similar for the heart in terms of oxygen requirement because ATP production from glucose is less oxygen-consuming than from FA. The regulation pathways for these shifts, which occur in physiologic as well as pathologic conditions (ischemia-reperfusion), are not yet known, although both insulin and pyruvate dehydrogenase activation are clearly involved. It becomes of strategic importance to clarify the pathways that control these shifts to influence the oxygen requirement of the heart. Excess FA oxidation is closely related to myocardial contraction disorders characterized by increased oxygen consumption for cardiac work. Such an increased oxygen cost of cardiac contraction was observed in stunned myocardium when the contribution of FA oxidation to oxygen consumption was increased. In rats, an increase in n-3 polyunsaturated FA in heart phospholipids achieved by a fish-oil diet improved the recovery of pump activity during postischemic reperfusion. This was associated with a moderation of the ischemia-induced decrease in mitochondrial palmitoylcarnitine oxidation. In isolated mitochondria at calcium concentrations close to that reported in ischemic cardiomyocytes, a futile cycle of oxygen wastage was reported, associated with energy wasting (constant AMP production). This occurs with palmitoylcarnitine as substrate but not with pyruvate or citrate. The energy wasting can be abolished by CoA-SH and other compounds, but not the oxygen wasting. Again, the calcium-induced decrease in mitochondrial ADP/O ratio was reduced by increasing the n-3 polyunsaturated FA in the mitochondrial phospholipids. These data suggest that in addition to the amount of circulating lipids, the quality of FA intake may contribute to heart energy regulation through the phospholipid composition. On the other hand, other intervention strategies can be considered. Several studies have focused on palmitoylcarnitine transferase I to achieve a reduction in beta-oxidation. In a different context, trimetazidine was suggested to exert its anti-ischemic effect on the heart by interfering with the metabolic shift, either at the pyruvate dehydrogenase level or by reducing the beta-oxidation. Further studies will be required to elucidate the complex system of heart energy regulation and the mechanism of action of potentially efficient molecules.

Adenosine Triphosphate↗
PubMed1996

Membrane docosahexaenoic acid vs. eicosapentaenoic acid and the beating function of the cardiomyocyte and its regulation through the adrenergic receptors.

The beta-adrenergic system in cardiac muscle cells is influenced by the n-3 polyunsaturated fatty acid (PUFA) content in cell membranes. This study deals with the specific effect of docosahexaenoic acid (DHA) as compared to other n-3 PUFA, without modification of the arachidonic acid content. Increasing the DHA content in the phospholipids of isolated cardiomyocytes did not provoke electrical or contraction modifications, except for a slightly lower plateau phase (-2 mV). Conversely, the beta-adrenergic function was affected at several levels: (i) the receptor affinity for dihydroalprenolol tended to decrease (Kd) without alteration of the number of beta-binding sites (beta max); (ii) the isoproterenol-induced (10(-7) M and 10(-6) M) cAMP production was significantly decreased (-20%); and (iii) the positive chronotropic response to beta-adrenergic stimulation (isoproterenol, 10(-7) M) was significantly enhanced (+80%). In order to further investigate the relationship between the decreased cAMP and the increased chronotropic response, the cells were treated with dibutyryl-cAMP, a permeant analogue of cAMP, which elicited a significantly higher chronotropic response in DHA-enriched cells than in EPA-enriched cells +50%). The increase in DHA content in cardiac cell membranes phospholipids may thus affect the beta-adrenergic system through an increase of cAMP efficiency. Although the membrane phosphatidylinositols were largely involved in the PUFA alterations, none of the parameters related to alpha-adrenergic system (chronotropic response, receptor density, affinity for prasozin, and inositide phosphate production) were influenced by the membrane DHA content.

Animals↗
PubMed1995

Trimetazidine: in vitro influence on heart mitochondrial function.

The mechanism of action of the antianginal trimetazidine (TMZ) remains largely unknown. In cultured rat ventricular myocytes in physiologic conditions, TMZ (5 x 10(-4) M) reduced the plateau potential level, the upstroke velocity, and the spontaneous action potential rate. When the cardiomyocytes were submitted to hypoxia (150 or 240 minutes) in a glucose-free medium, treatment with TMZ largely prevented the hypoxia-induced electromechanical alterations, i.e., the decrease in plateau amplitude, in resting membrane potential, in action potential duration, in rate, and in contractility. No hypoxia-induced arrhythmia was observed in the TMZ-treated cells. Moreover, the lactate dehydrogenase leakage was significantly reduced in the TMZ-treated cardiomyocytes (-58% and -36%, after 150 and 240 minutes of hypoxia, respectively). The drug was not efficient in reducing the hypoxia-induced decrease in adenosine triphosphate (ATP) content. The cellular ATP content was slightly lower in the TMZ-treated cells in normoxic conditions and in hypoxic conditions, but only in the glucose-free medium. To investigate further the relation between TMZ and energy metabolism, the respiration parameters were measured in heart mitochondria isolated from control and TMZ-treated rats (6 mg/kg/day, 7 days) with different substrates. This treatment resulted in a slight alteration of pyruvate oxidation, which was observed in the absence and in the presence of TMZ (10(-4) M) in the respiration medium. Conversely, a potent inhibition of palmitoylcarnitine oxidation was measured when TMZ was added to the respiration medium. Neither pretreatment of the rats, nor addition of TMZ to the medium affected the oxidation of glutamate or citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

Effect of docosahexaenoic acid and eicosapentaenoic acid in the phospholipids of rat heart muscle cells on adrenoceptor responsiveness and mechanism.

The specific effect of docosahexaenoic (DHA; C22:6 n-3), as compared to eicosapentaenoic acid (EPA; C20:5 n-3), on adrenoceptor function was investigated in cultured rat myocardial cells. The cardiomyocytes were grown for 24 h in a conventional seric medium, and then incubated for 96 h in a medium enriched with either DHA or EPA. After this treatment, the phospholipids of the DHA-treated cells contained approximately 20% of the total fatty acids as C22:6 n-3, and those of EPA-treated cells displayed a high content in C20:5 n-3 and its elongation product C22:5 n-3 (30% of total fatty acids). Additionally, the n-3/n-6 polyunsaturated fatty acid ratio was the same in the two groups of cells. These modifications were roughly similar in all the phospholipid classes. The contractions were monitored photometrically and no significant difference in basal frequency and contraction parameters could be detected. The stimulation of the beta-adrenergic receptors (isoproterenol 10(-7) M) resulted in a positive chronotropic effect, which was significantly higher in the DHA-rich cells. Conversely, the higher DHA content in the phospholipids appeared to induce a decrease in the affinity of the beta-receptors for the ligand (dihydroalprenolol) without alteration of the number of beta-receptor binding sites and provoked a significant decrease in isoproterenol-stimulated cAMP production (-19%). To investigate further these controversial data, the cardiomyocytes were treated with dibutyryl-cAMP, which elicited a positive chronotropic response significantly higher in the DHA-rich cells. The alpha-adrenergic stimulation by phenylephrine (3 x 10(-6) M) increased the spontaneous rate, but in a similar manner in the DHA- and EPA-enriched cells. Similarly, neither the alpha-adrenergic receptor binding characteristics nor the production of phosphoinositides was modulated by the membrane DNA content, although the phosphatidylinositol PUFAs were significantly altered. In conclusion, increasing the DHA content in membrane phospholipids did not affect the alpha-adrenergic system, but exerted a specific positive influence on the beta-adrenergic transduction mechanism, essentially through an increase of cAMP efficiency.

Animals↗
PubMed1995

Developmental differences in distribution of cyclic nucleotide phosphodiesterase isoforms in cardiomyocytes and the ventricular tissue from newborn and adult rats.

We characterized cyclic nucleotide phosphodiesterase (PDE) activities in neonatal rat cardiomyocytes and in whole ventricle from newborn and adult rats, to determine whether cyclic nucleotide hydrolytic activities might be influenced by the developmental stage of the animal or by cell isolation and culture procedures. Using anion-exchange high-performance liquid chromatography (HPLC), we obtained four soluble PDE activities from adult rat ventricle. Peak 1, a cyclic GMP-specific PDE was stimulated by Ca2+/calmodulin; peak 2 hydrolyzed cyclic AMP and cyclic GMP, the addition of cyclic GMP stimulating the hydrolysis of cyclic AMP. Peaks 3 and 4 selectively hydrolyzed cyclic AMP, peak 3 being very sensitive to inhibition by rolipram and peak 4 consisting of two different enzyme activities, one inhibited by cyclic GMP (peak 4b) and the other inhibited by rolipram (peak 4a). In cardiomyocytes and whole ventricle from newborn rats, the response of the two cyclic GMP-sensitive PDE isoforms (cyclic GMP-stimulated and cyclic GMP-inhibited PDE) to the effector cyclic GMP was markedly reduced as compared with that of the corresponding isoforms (peaks 2 and 4b) present in the heart ventricle of adult rats. The other peaks were analogous to peaks 1, 3, and 4a of the whole ventricle. The profile of PDE activities in nonmyocardial cells did not differ from that of myocytes. Therefore, the lack of cyclic GMP effects was not due to culture conditions. Differences in PDE activities observed between cardiomyocytes from newborn rats and ventricle from adult rats might be age dependent.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Eicosanoid synthesis in cardiomyocytes: influence of hypoxia, reoxygenation, and polyunsaturated fatty acids.

The synthesis of eicosanoids was investigated in cultured rat ventricular myocytes. Under normoxia, the cardiomyocytes released 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin (PG) E2 and smaller amounts of PGF2 alpha and thromboxane B2. Hypoxia enhanced the production of PGE2 and PGF2 alpha, whereas the synthesis of 6-keto-PGF1 alpha was not affected. Conversely, posthypoxic reoxygenation greatly increased the synthesis of 6-keto-PGF1 alpha, whereas the synthesis of PGF2 alpha, was not affected and that of PGE2 was reduced. The cardiomyocyte polyunsaturated fatty acid (PUFA) profile was altered by arachidonic acid or eicosapentaenoic acid and docosahexaenoic acid. Under normoxia, the eicosanoid production appeared to be roughly related to the cell phospholipid arachidonic acid content. Conversely, during posthypoxic reoxygenation, the production of eicosanoids was related to the cell phospholipid n-3 PUFA content, with the n-3-rich cells displaying a marked inhibition of the synthesis. This inhibition was mainly attributed to eicosapentaenoic acid and/or docosapentaenoic acid. Whether this inhibition occurs in vivo during postischemic reperfusion, it may contribute to the beneficial effect of n-3 PUFA on the heart.

Aerobiosis↗
PubMed1995

Influence of the phospholipid content in docosahexaenoic acid on electrophysiology and contraction of rat heart muscle cells.

The cardiovascular beneficial effects of fish oils are currently attributed to docosahexaenoic (C22:6 n-3) and eicosapentaenoic (C20:5 n-3) acids, although most investigations have focused on eicosapentaenoic acid. This study was devoted to the specific effect of docosahexaenoic acid, as compared to eicosapentaenoic acid, on the basal electrophysiological and mechanical characteristics of cultured rat myocardial cells. The myocyte cultures were prepared from newborn rat heart ventricles. The cells were grown for 24 hours in a conventional seric medium, and then incubated in a medium enriched with either docosahexaenoic acid or eicosapentaenoic acid for 96 hours. This treatment resulted in docosahexaenoic acid-rich cells (16% of the phospholipid fatty acids) and docosahexaenoic acid-poor cells (1.5%), both displaying the same phospholipid n-6/n-3 polyunsaturated fatty acid ratio. The transmembrane potentials were recorded with glass microelectrodes. Contractions were monitored photometrically. The action potential amplitude was slightly smaller in docosahexaenoic acid-rich cells (-4 mv), due to a lower plateau phase. There was no difference in action potential duration and spontaneous rate. The contraction measurements were not significantly different between the two groups of cells. We conclude that increasing the docosahexaenoic acid content in cardiomyocyte membrane phospholipids may have modulated the calcium ionic channels governing the plateau phase of the action potential, whereas the other physiological activities remained unaffected.

Animals↗
PubMed1994

Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia.

The influence of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on heart pump function and mitochondrial energy metabolism was investigated before and after ischemia. Weanling male Wistar rats were fed for 8 weeks a diet containing either 10% of sunflower seed oil (SSO group) or 10% of a 1:1 (w/w) mixture of fish oil and sunflower seed oil (FO group). The hearts were perfused according to the working mode for 15 min with a Krebs-Henseleit medium containing glucose (11 mM), insulin (10 IU/L) and caprylic acid (25 microM). They were then either maintained in normoxic conditions (70 min) or subjected to a global no-flow normothermic ischemia (20 min) followed by reperfusion (50 min). The aortic and coronary flows were monitored at 5-min intervals. The lactate dehydrogenase (LDH) release in the coronary effluent was evaluated in the control hearts and during ischemia/reperfusion. At the end of the perfusion, two subpopulations of mitochondria were prepared from each heart, by either mechanical or enzyme extraction (ME and EE mitochondria, respectively). The succinate dehydrogenase (SDH) activity was evaluated. Furthermore, the respiration parameters were assessed with either glutamate (20 mM) or palmitoylcarnitine (25 microM) as substrate. Substituting sunflower seed oil by fish oil in the diet provoked a large decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. The n-3 PUFA enrichment did not alter the coronary and aortic flows nor the LDH release in physiological conditions. Conversely, during post-ischemic reperfusion, the increased amount of n-3 PUFA improved the recovery of aortic flow and decreased the LDH release, without affecting significantly the coronary flow. In ME and EE mitochondria, the phospholipid n-6/n-3 PUFA ratio was similarly modified by the dietary manipulations. The analysis of total cardiac SDH activity suggested an ischemia-induced oedema, of similar magnitude in the two dietary groups. However, neither dietary manipulations nor ischemia influenced the mitochondrial extraction. Similarly, the parameters of glutamate oxidation were also unaffected. Conversely, with palmitoylcarnitine, post-ischemic reperfusion induced a decrease in both state III respiration rate and energy production which were more important in the EE mitochondria of the SSO group. These results suggest that the recovery of mitochondrial energy metabolism and myocardial pump function during reperfusion may be improved in n-3 PUFA-rich hearts. This could be related to a lower injury in n-3 PUFA-rich membranes. Since cardiac function in physiological conditions was not affected by the diet, fish oil could be considered as a beneficial factor to limit heart injury during ischemia and reperfusion.

Animals↗
PubMed1994

Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation.

This study was undertaken to evaluate the direct cardioprotective effect of trimetazidine (TMZ), an anti-anginal drug devoid of haemodynamic action, on isolated myocytes. Cultured rat ventricular myocytes were treated with the drug 16 h and 1 h before the experiments. The drug-treated cells and control cells were placed in a substrate free medium and submitted in a specially designed device to either normoxia (N4), or hypoxia (150 min, H2.5, or 240 min, H4), or 150 min hypoxia followed by 90 min reoxygenation (HR). The treatment of the cells with TMZ (5 x 10(-4) M) resulted in a significant decrease of lactate dehydrogenase (LDH) leakage (-58% in H2.5, -36% in H4 and -37% in HR). The LDH release provoked by oxidizing agents. H2O2 and 13-s-HpOTrE (13(S)-hydroperoxyoctadecatrienoic acid) during post-hypoxic reoxygenation was also lowered by TMZ. However, this effect reflected the beneficial action of TMZ during hypoxia since the drug was not efficient in altering the LDH leakage induced by the oxidizing agents in normal conditions. Moreover, the hypoxia-induced decrease of ATP content was not affected by TMZ, and resynthesis of ATP during substrate-free reoxygenation was similar in TMZ-treated and control cells. The respiration parameters have been studied in rat heart mitochondria isolated from control and TMZ-treated rats, in the presence or absence of TMZ in the respiration medium (10(-4) M). The main result was a rapid and potent inhibition of palmitoylcarnitine oxidation, when TMZ was added to the respiration medium. The chronic treatment only resulted in a slight alteration of pyruvate oxidation. In conclusion, a pre-treatment of ventricular myocytes with TMZ resulted in an increased cell resistance to hypoxic stress, as evidenced by LDH leakage. This cytoprotective effect of TMZ should not be mediated through an antioxidant activity, but could be related to a modification of lipid metabolism.

Adenine Nucleotides↗
PubMed1993

Anthracycline toxicity is potentiated by iron and inhibited by deferoxamine: studies in rat heart cells in culture.

The interrelation between iron, iron chelation, and anthracycline toxicity was investigated in a heart cell culture system. Two indicators of cellular damage have been used, lactate dehydrogenase (LDH) release and cell contractility. Both of these indicators have shown a marked increase in doxorubicin toxicity by prior iron loading. This was not a simple additive effect, because at the concentrations used, iron had only a minimal effect on LDH release and no effect at all on contractility, whereas doxorubicin had only a minor effect on contractility. Deferoxamine (DF) treatment of iron-loaded heart cells resulted in a marked decrease in anthracycline toxicity as judged both by LDH leakage and cell contractility. However, DF treatment of normal heart cells had no measurable protective effect against doxorubicin toxicity, whether DF was administered before or simultaneously with doxorubicin. Doxorubicin treatment did not alter cellular malondialdehyde (MDA) concentrations in either normal or iron-loaded cells. Conversely, the protective effect of DF in iron-loaded cells and its failure to prevent anthracycline toxicity in normal cells were both associated with a significant decrease in MDA measurements. Our data indicate that iron overload aggravates anthracycline toxicity and that this interaction may be prevented by effective iron chelating therapy. Because patients requiring anthracycline therapy often have increased tissue iron stores caused by multiple blood transfusions and bone marrow suppression, our observations may have important implications for the prevention of anthracycline toxicity.

Animals↗
PubMed1992

Eicosapentaenoic and docosahexaenoic acids in cultured rat ventricular myocytes and hypoxia-induced alterations of phospholipase-A activity.

Hypoxia was reported to induce a decrease in phosphatidylcholine-hydrolyzing phospholipase activity (PC-PLA) in cultured rat cardiomyocytes. This work was intended to compare the influence of the presence of either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in the phospholipids on the PC-PLA activity in normoxic and hypoxic conditions. The enrichment of the medium with EPA or DHA resulted in cell phospholipids containing about 2% or 22% DHA, respectively. These cells were then submitted for 3.5 h to either normoxia or hypoxia and the PC-PLA activities were assayed using [1-14C] dioleoyl-PC (pH 8.4 for PC-PLA2 and 4.9 for PC-PLA1). The results show that both enzymic activities are significantly higher in DHA-rich cardiomyocytes. Hypoxia induced a significant decrease in PC-PLA2 (about 25%) which was not statistically different between the two groups of cells. The hypoxia-induced decrease in PC-PLA1 was not found significant. In conclusion, the nature of the long chain n-3 polyunsaturated fatty acids in the phospholipids appears to contribute to the regulation of PC-PLA activity but not to influence its decrease during hypoxia.

Animals↗
PubMed1992

Incorporation of cyclic fatty acid monomers in lipids of rat heart cell cultures.

Primary cultures of newborn rat cardiomyocytes were grown in medium supplemented with cyclic fatty acid monomers (CFAM) which had been isolated from heated linseed oil. The cells were harvested, and lipids were extracted and fractionated using silica cartridges and high-performance liquid chromatography. The CFAM structures isolated from cellular lipids were determined and compared to those that had been supplemented to the medium, using gas-liquid chromatography coupled with mass spectrometry (GC/MS). We found that CFAM were incorporated into phospholipids and neutral lipids of cardiomyocytes. Furthermore, CFAM with a cyclopentyl ring structure were more abundant in cardiomyocytes than were the cyclohexyl ring isomers. Our data suggest that CFAM of the 5-carbon and 6-carbon ring series are metabolized differently in newborn rat cardiomyocytes.

Animals↗
PubMed1992

Polyunsaturated fatty acids in cultured cardiomyocytes: effect on physiology and beta-adrenoceptor function.

This study was carried out to investigate the influence of the membrane fatty acid composition on the basal electrical and contractile activities and the response to beta-adrenergic stimulation of rat cardiac muscle cells in culture. Cells were grown for 3 days in a conventional serum culture medium and then incubated for 24 h in synthetic media containing either n-6 or n-3 as the sole source of polyunsaturated fatty acids (PUFA). The n-6/n-3 ratio in the phospholipids was 0.9 in the n-3 cells and 13.1 in the n-6 cells compared with 6.3 in controls cells. Such modifications did not alter action potentials and the main parameters related to contraction, although shortening was slightly accelerated in the n-6 cells. On the other hand, the positive chronotropic effect induced by isoproterenol was more pronounced (P less than 0.01) in n-3 cells than in n-6 cells. In addition, isoproterenol caused a decrease in contraction duration and in shortening and relaxation time that was less pronounced in n-6 than in control cells (P less than 0.01, P less than 0.01 and P less than 0.05, respectively). These results suggest that the PUFA balance in the phospholipids may contribute to modulate the cardiac adrenergic receptor system but not the membrane properties related to electro-mechanical functions.

Animals↗
PubMed1991

Influence of dietary linseed oil and sunflower seed oil on some mechanical and metabolic parameters of isolated working rat hearts.

The role played by membrane lipid environment on cardiac function remains poorly defined. The polyunsaturated fatty acid profile of myocardial phospholipids could be of utmost importance in the regulation of key-enzyme activities. This study was undertaken to determine whether selective incorporation of n-6 or n-3 fatty acids in membrane phospholipids might influence cardiac mechanical performances and metabolism. For 8 wk, male weaning Wistar rats were fed a semi-purified diet containing either 10% sunflower seed oil (72% C18:2 n-6) or 10% linseed oil (54% C18:3 n-3) as the sole source of lipids. The hearts were then removed and perfused according to working mode with a Krebs-Henseleit buffer containing glucose (11 mM) and insulin (10 Ul/l). Cardiac rate, coronary and aortic flows and ejection fraction were monitored after 30 min of perfusion. Myocardial metabolism was estimated by evaluating the intracellular fate of 1-14C palmitate. Sunflower seed oil and linseed oil feeding did not modify either coronary or aortic flow, which suggests that cardiac mechanical work was not affected by the diets. Conversely, cardiac rate was significantly decreased (-18%; P less than 0.01) when rats were fed the n-3 polyunsaturated fatty acid rich diet. Radioanalysis of the myocardial metabolism suggested that replacing n-6 polyunsaturated fatty acids by n-3 polyunsaturated fatty acids: i) did not alter palmitate uptake; ii) prolonged palmitate incorporation into cardiac triglycerides; iii) reduced beta-oxidation of palmitic acid. These results support the assumption that dietary fatty acids, particularly n-6 and n-3 fatty acids, play an important role in the regulation of cardiac mechanical and metabolic activity.

Animals↗
PubMed1991

Fatty acids of hearts from rats fed linseed or sunflower oil and of cultured cardiomyocytes grown on their sera.

Rats were fed for 6 weeks a diet containing either sunflower oil or linseed oil. In each case, blood serum was subsequently collected and added to two media which were then used to grow cardiomyocytes. Under these conditions, the incorporation of omega 6 and omega 3 polyunsaturated fatty acids shows similar trends in hearts and cultured cardiomyocytes. The content of C22-unsaturated fatty acids was lower in the myocytes than in the hearts but the ratio of acids of the omega 6 series to those of the omega 3 series was similar.

Animals↗