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a1-adrenergic response of rat cardiomyocytes aged in culture can be modulated by the manipulation of lipid composition
216
EFA & Eicosanoids 1997 - Edinburgh
Poster Presentations Monday 21 July
PIO
P9
Absence of Atherosclerosis in Intramyocardial Coronary Arteries and its Relationship to Mural Stress. Rebicsek, F., M.D., Thubrikar, M.J., Ph.D., Heineman Research Laboratory, Carolinas Medical Center, Charlotte, NC USA.
Abstract
Withdrawn
]
Occurrence of atherosclerotio lesions was studied in both epioardial and intramyoeardial coronary arteries in 150 patients undergoing coronary bypass surgery. Most patients showed diffuse coronary arteriosclerosis. In 17 patients the left'circumflex coronary artery gave off branches whose distal portions ran entirely intramyocardially. Of these, 15 had no atherosclerosis in the intramyocardial portions whereas the same arteries epicardially had lesions, 1 had a calcified plaque, and 1 had a recanalized thrombus. The reason why intramyoeardial arteries are immune to atherosclerosis was studied in animal experiments. The intramyocardial pressures (IMP) were measured in 8 canine hearts. The pressures were measured with a micro-tip catheter which had a tiny recessed pressure sensor. The IMP was measured on the lateral wall of the left ventricle (LV) and at the apex. It was measured within the myocardium at 3 depths: Near the epieardium, in the mid wall, and near the endocardium. The left ventricular cavity pressure was also measured simultaneously using a fluid filled catheter. The myocardium developed significant pressures within the muscle mass throughout the cardiac cycle. The IMP in the epicardial region was the lowest, in the i'nid wall it was higher, and in the endoeardia] region it was the highest. Subepieardial systolic pressures were as high as 30-80% of the LV cavity systolic pressures. Mid-wall systolic pressures were 79 + 7% of the LV cavity systolic pressures. Subendoeardial systolic pressures were generally higher (104 + 7%) than the LV cavity systolic pressures. High systolic IMP indicates that the pressure gradient aeross the intramyocard[al coronary artery wall is significantly reduced, and sometimes the gradient may even be eliminated or reversed. Hence, the intramyocardial arteries experience less pressure gradient and therefore lower mural stress in systole compared to the epicardial arteries. In conclusion, the absence of atherosclerosis in the intramyocardial coronary arteries appears to be due to reduced mural stress, i.e. the lowering or absence of the transmural pressure gradient.
Pll
P12
A COMBINATION OF 0J6/t03 FATTY ACIDS DECREASES BLOOD PRESSURE IN GENETIC HYPERTENSIVE RAT. GERMAIN S., NARCE M., POISSON J.-P. Units de Nutrition Cellulaire et Mrtabolique, Universit4 de Bourgogne, Dijon, France.
al-adrenergic response of rat cardiomyocytes aged in culture can be modulated by the manipulation of lipid composition.
The purpose of the present study was to investigate the effect of a concentrated preparation (GLAS0/EPA30) containing gammalinolenic, eicosapentaenoic and docosahexaenoic acids on blood pressure in adult Spontaneously Hypertensive Rat (SHR). 18 week old SHR were divided into two groups : the control group received a standard semi-synthetic diet, and the experimental group the standard diet plus 0.42 % of GLA 80 and 0.9 % of EPA 30 for 13 weeks. Blood pressure was measured by a non bloody method at different times of the experiment. The fatty acid composition of kidney, heart and isolated hepatocyte total lipids were determined by GLC at the end of the experiment. In vitro PUFA biogenesis was investigated by incubation of isolated hepatocytes in presence of [IJ4C] 18 : 2 n-6, 18 : 3 n-3 and 20 : 3 n-6 as substrates. The conversion of substrates into products of desaturation was estimated by measuring the distribution of radioactivity after RPLC partition. The blood pressure of experimental rats was significantly lower than controls from 8 weeks (186_+5 versus 200_+5 mm Hg) of diet. Kidney and heart 20:4n-6 was significantly decreased in experimental group (-20% and -15% respectively), when GLA, EPA and DHA contents were significantly increased. A6 n-6 and n-3 and A5 n-6 desaturase activities were significantly lower (-33%, -24% and - 18% respectively) in the GLA/EPA/DHA supplemented group. These results pointed out that GLAS0/EPA30 may be considered as an active pharmacological nutrient lowering blood pressure, in adult SHR. The effects of this combination seem to be mediated via changes in the EFA metabolic cascade, and in the target organs composition in PUFA precursors of prostaglandins involved in blood pressure regulation.
Lorenzini A., Bordoni A., Horrobin D.F.*, Biagi P.L., Hrelia S. Dept. Biochem Univ. Bologna Cltaly),*EfamolIRes. Inst. Kentvitle (Canada).
The fatty acid composition of the phosphoinositides (Ptdlns) was evaluated by gas chromatography in cultured neonatal rat cardiomyocytes during the aging-like process "in vitro", comparing data obtained from control and gamma-linolenic acid (GLA) supplemented cardiomyocytes. The response to cq-stimulation was evaluated in both control and supplemented cells as inositol phosphate (IPn) production in [3H]-inositol prelabeled cells. We verified the relationship between the alterations of the PtdIns fatty acid composition concomitant to culture aging and the cell response to exogenous stimuli. Arachidonate level decreased as a function of age in all the PtdIns, which appeared to be more saturated as cells aged in culture. IPn production in response to ~ stimulation decreased as cells aged in culture. Supplementation of culture medium with GLA caused significant modifications in the fatty acid pattern of the PtdIns, which appeared less saturated than the corresponding fractions isolated from unsupplemented cells during the aging-like process. The modifications induced by the supplementation in the PtdIns fatty acid composition prevented the age-related reduction of IPn production upon stimulation. These results clearly indicate a major role for the lipid composition in determining the response to cq-stimulation, suggesting a nutritional approach to overcome some of the impairments of molecular events related to the process of aging.
EFA & Eicosanoids 1997 - Edinburgh
Poster Presentations Monday 21 July
PIO
P9
Absence of Atherosclerosis in Intramyocardial Coronary Arteries and its Relationship to Mural Stress. Rebicsek, F., M.D., Thubrikar, M.J., Ph.D., Heineman Research Laboratory, Carolinas Medical Center, Charlotte, NC USA.
Abstract
Withdrawn
]
Occurrence of atherosclerotio lesions was studied in both epioardial and intramyoeardial coronary arteries in 150 patients undergoing coronary bypass surgery. Most patients showed diffuse coronary arteriosclerosis. In 17 patients the left'circumflex coronary artery gave off branches whose distal portions ran entirely intramyocardially. Of these, 15 had no atherosclerosis in the intramyocardial portions whereas the same arteries epicardially had lesions, 1 had a calcified plaque, and 1 had a recanalized thrombus. The reason why intramyoeardial arteries are immune to atherosclerosis was studied in animal experiments. The intramyocardial pressures (IMP) were measured in 8 canine hearts. The pressures were measured with a micro-tip catheter which had a tiny recessed pressure sensor. The IMP was measured on the lateral wall of the left ventricle (LV) and at the apex. It was measured within the myocardium at 3 depths: Near the epieardium, in the mid wall, and near the endocardium. The left ventricular cavity pressure was also measured simultaneously using a fluid filled catheter. The myocardium developed significant pressures within the muscle mass throughout the cardiac cycle. The IMP in the epicardial region was the lowest, in the i'nid wall it was higher, and in the endoeardia] region it was the highest. Subepieardial systolic pressures were as high as 30-80% of the LV cavity systolic pressures. Mid-wall systolic pressures were 79 + 7% of the LV cavity systolic pressures. Subendoeardial systolic pressures were generally higher (104 + 7%) than the LV cavity systolic pressures. High systolic IMP indicates that the pressure gradient aeross the intramyocard[al coronary artery wall is significantly reduced, and sometimes the gradient may even be eliminated or reversed. Hence, the intramyocardial arteries experience less pressure gradient and therefore lower mural stress in systole compared to the epicardial arteries. In conclusion, the absence of atherosclerosis in the intramyocardial coronary arteries appears to be due to reduced mural stress, i.e. the lowering or absence of the transmural pressure gradient.
Pll
P12
A COMBINATION OF 0J6/t03 FATTY ACIDS DECREASES BLOOD PRESSURE IN GENETIC HYPERTENSIVE RAT. GERMAIN S., NARCE M., POISSON J.-P. Units de Nutrition Cellulaire et Mrtabolique, Universit4 de Bourgogne, Dijon, France.
al-adrenergic response of rat cardiomyocytes aged in culture can be modulated by the manipulation of lipid composition.
The purpose of the present study was to investigate the effect of a concentrated preparation (GLAS0/EPA30) containing gammalinolenic, eicosapentaenoic and docosahexaenoic acids on blood pressure in adult Spontaneously Hypertensive Rat (SHR). 18 week old SHR were divided into two groups : the control group received a standard semi-synthetic diet, and the experimental group the standard diet plus 0.42 % of GLA 80 and 0.9 % of EPA 30 for 13 weeks. Blood pressure was measured by a non bloody method at different times of the experiment. The fatty acid composition of kidney, heart and isolated hepatocyte total lipids were determined by GLC at the end of the experiment. In vitro PUFA biogenesis was investigated by incubation of isolated hepatocytes in presence of [IJ4C] 18 : 2 n-6, 18 : 3 n-3 and 20 : 3 n-6 as substrates. The conversion of substrates into products of desaturation was estimated by measuring the distribution of radioactivity after RPLC partition. The blood pressure of experimental rats was significantly lower than controls from 8 weeks (186_+5 versus 200_+5 mm Hg) of diet. Kidney and heart 20:4n-6 was significantly decreased in experimental group (-20% and -15% respectively), when GLA, EPA and DHA contents were significantly increased. A6 n-6 and n-3 and A5 n-6 desaturase activities were significantly lower (-33%, -24% and - 18% respectively) in the GLA/EPA/DHA supplemented group. These results pointed out that GLAS0/EPA30 may be considered as an active pharmacological nutrient lowering blood pressure, in adult SHR. The effects of this combination seem to be mediated via changes in the EFA metabolic cascade, and in the target organs composition in PUFA precursors of prostaglandins involved in blood pressure regulation.
Lorenzini A., Bordoni A., Horrobin D.F.*, Biagi P.L., Hrelia S. Dept. Biochem Univ. Bologna Cltaly),*EfamolIRes. Inst. Kentvitle (Canada).
The fatty acid composition of the phosphoinositides (Ptdlns) was evaluated by gas chromatography in cultured neonatal rat cardiomyocytes during the aging-like process "in vitro", comparing data obtained from control and gamma-linolenic acid (GLA) supplemented cardiomyocytes. The response to cq-stimulation was evaluated in both control and supplemented cells as inositol phosphate (IPn) production in [3H]-inositol prelabeled cells. We verified the relationship between the alterations of the PtdIns fatty acid composition concomitant to culture aging and the cell response to exogenous stimuli. Arachidonate level decreased as a function of age in all the PtdIns, which appeared to be more saturated as cells aged in culture. IPn production in response to ~ stimulation decreased as cells aged in culture. Supplementation of culture medium with GLA caused significant modifications in the fatty acid pattern of the PtdIns, which appeared less saturated than the corresponding fractions isolated from unsupplemented cells during the aging-like process. The modifications induced by the supplementation in the PtdIns fatty acid composition prevented the age-related reduction of IPn production upon stimulation. These results clearly indicate a major role for the lipid composition in determining the response to cq-stimulation, suggesting a nutritional approach to overcome some of the impairments of molecular events related to the process of aging.