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The positive role of lipid peroxidation: Regression of hypertrophied myocardium
J Mol Cell Cardiol 21 (Supplement
III) (1989)
MAGGERATED DIASTOLIC DYSFUNCTIONOF HYPERTENSIVE HYPEKTROPHIED MYOCARDIUM DURING HYPOXIA. C.S. Apstein, W.M. Vogel, E.O. Weinberg, M.J. Cunningham, L.F. Wexler, W.N. Grice, J.S.Ingwall, B.H. Lorell. Boston and Harvard Universities, Boston, MA, USA. In hypertrophied hearts from rats with hypertension (DOC/Na model) LVEDP increased much more than in age-matched controls during isolated isovolunic (balloon-in-LV) hwoxic wrfusion at constant coronary flow. ‘Ihis exaggerated hy&xic*&astolic dysfunction of the LVH hearts-was not due to different myocardial contents or rates of decrease of glycogen, ATP, or creatine phosphate during hypoxia. However, the LVH hearts had 40% less nlvcolvtic flux (lactate production) than controls during hypoxia with 5.5 Z glLcose perfusion. -High glucose (27.5 IrM) and -in&in perfusion restored control values of hypoxic glycolytic flux and LVEDP in the LVH Diltiazem (150 nM) also inhibited the exaggerated diastolic groupdysfunction of the LVH g&p. A low Na diet reversed the hypertension, regressed the LVH, and restored the exaggerated diastolic dysfunction and reduced glycolytic flux of the LVH group to control levels. These results suggest that reversible alterations of glycolytic metabolism and calciun regulation make the hypertrophied myocardiun more vulnerable to hypoxic diastolic dysfunction.
TIIE POSITIVE MYOCARDIUM.
ROLE Yuri
OF LIPID PEROXIDATION: V.
Arkhipenko.
Institute
REGRESSION OF IIYPERTROPIUED of
General Pathology and Pathophysiology, USSR. The regression of hypertrophied heart presupposes disassembling of all cardio-myocyte components including membrane structures. It was studied the involvement of free radical oxidation of membrane phospholipids in the cardiac regression. Altitude hypprtrophy was developed in barocamera (6000 m, 6 hours daily). Two weeks of pertodical hypoxia leads to l,S-fold increasing of heart weight (right ventricle weight was Z-fold increased). In 7-10 days after adaptation the heart weight reduced to normal. Both the development and regression of myocardial hypertrophy was accompanied by changes in Mb and Hh organ concrntratlons proportlonal to weight changes. In lipid extracts of maximal hyprtrophled heart, the BOX decrease of llpid peroxldation product ( d iene conjugated regularly occured. The rate of regression had negative correlation wi th peroxidation products accumulation. lntraperitoneal injection of fret radical scaven grr MIT attenuate the regression rate. The results suggests that unlikt the common knowledge about the membrane injury effect, lipid peroxidatlon can play the positive role in disassembling of superfluous cell membrane structures. Moscow,
SARCOPLASMIC RETICULUM Caz+ ATPase IN PRESSURE OVERLOAD IN THE RAT: FUNCTION AND GENE EXPRESSION .Diane de la Bastie’, Dmitri Levitsky+, Lydie Rappaport’, Jean-Jacques Mercadier’. Franpoise Marotte’, Claudine Wisnewsky’,Victor Brovkovich+. Keity Schwartz*, Anne Marie LomprB’.‘INSERM U 127, Hbpital Lariboisihre, 41 Bd de la Chapelle, 75010 Paris, France.+lnstitute of Experimental Cardiology, USSR Cardiology Research Center, 3rd Cherepkovskaya Street 15A, Moscow 121552 USSR. To investigate the effect of chronic pressure overload on cardiac sarcoplasmic reticulum, we measured on crude tissue homogenates, the oxalate stimulated Ca2+ uptake, the level of Ca2+ dependent phosphorylated intermediate, the total amount of Ca2+ pumps (determined using a specific monoclonal antibody) and of the corresponding mRNA (using a rat heart Ca2+ ATPase cDNA). As compared to shams the Ca2+ uptake declined in mild and severe hypertrophy (from 12.1 * 1.2 nmoles Caz+/mg protein/min to 9.1 i 1.5 and 6.7 * 1 .l respectively ).The level of Ca2+ dependent phosphotylated intermediate is also depressed :from 69.7 It 8.2 in shams to 58.8 * 7.4 and 48.1 f 13.5 pmoles Plmg protein in mild and severe hypertrophy respectively. Using Sl nuclease mapping, we observed that the Ca2+ ATPase mRNA from sham-operated and hyperlrophied hearts were identical. Finally, the concentrations of Ca 2+ ATPase mRNA and protein in the left ventricle were unchanged in mild hypertrophy while in severe hypertrophy it decreased respectively to 68.7 ?I 12.9% and 80.1 f 15.5% of the amount measured in shams.The total amount of mRNA and enzyme per left ventricle was either unchanged or sliihtly increased. The stow velocity of relaxation of severely hypertrophied heart can be. at least partially, explained by the absence of an increase in the expression of the Ca 2* ATPase gene and by the relative diminution in the density of the Ca2* pumps. s.2
III) (1989)
MAGGERATED DIASTOLIC DYSFUNCTIONOF HYPERTENSIVE HYPEKTROPHIED MYOCARDIUM DURING HYPOXIA. C.S. Apstein, W.M. Vogel, E.O. Weinberg, M.J. Cunningham, L.F. Wexler, W.N. Grice, J.S.Ingwall, B.H. Lorell. Boston and Harvard Universities, Boston, MA, USA. In hypertrophied hearts from rats with hypertension (DOC/Na model) LVEDP increased much more than in age-matched controls during isolated isovolunic (balloon-in-LV) hwoxic wrfusion at constant coronary flow. ‘Ihis exaggerated hy&xic*&astolic dysfunction of the LVH hearts-was not due to different myocardial contents or rates of decrease of glycogen, ATP, or creatine phosphate during hypoxia. However, the LVH hearts had 40% less nlvcolvtic flux (lactate production) than controls during hypoxia with 5.5 Z glLcose perfusion. -High glucose (27.5 IrM) and -in&in perfusion restored control values of hypoxic glycolytic flux and LVEDP in the LVH Diltiazem (150 nM) also inhibited the exaggerated diastolic groupdysfunction of the LVH g&p. A low Na diet reversed the hypertension, regressed the LVH, and restored the exaggerated diastolic dysfunction and reduced glycolytic flux of the LVH group to control levels. These results suggest that reversible alterations of glycolytic metabolism and calciun regulation make the hypertrophied myocardiun more vulnerable to hypoxic diastolic dysfunction.
TIIE POSITIVE MYOCARDIUM.
ROLE Yuri
OF LIPID PEROXIDATION: V.
Arkhipenko.
Institute
REGRESSION OF IIYPERTROPIUED of
General Pathology and Pathophysiology, USSR. The regression of hypertrophied heart presupposes disassembling of all cardio-myocyte components including membrane structures. It was studied the involvement of free radical oxidation of membrane phospholipids in the cardiac regression. Altitude hypprtrophy was developed in barocamera (6000 m, 6 hours daily). Two weeks of pertodical hypoxia leads to l,S-fold increasing of heart weight (right ventricle weight was Z-fold increased). In 7-10 days after adaptation the heart weight reduced to normal. Both the development and regression of myocardial hypertrophy was accompanied by changes in Mb and Hh organ concrntratlons proportlonal to weight changes. In lipid extracts of maximal hyprtrophled heart, the BOX decrease of llpid peroxldation product ( d iene conjugated regularly occured. The rate of regression had negative correlation wi th peroxidation products accumulation. lntraperitoneal injection of fret radical scaven grr MIT attenuate the regression rate. The results suggests that unlikt the common knowledge about the membrane injury effect, lipid peroxidatlon can play the positive role in disassembling of superfluous cell membrane structures. Moscow,
SARCOPLASMIC RETICULUM Caz+ ATPase IN PRESSURE OVERLOAD IN THE RAT: FUNCTION AND GENE EXPRESSION .Diane de la Bastie’, Dmitri Levitsky+, Lydie Rappaport’, Jean-Jacques Mercadier’. Franpoise Marotte’, Claudine Wisnewsky’,Victor Brovkovich+. Keity Schwartz*, Anne Marie LomprB’.‘INSERM U 127, Hbpital Lariboisihre, 41 Bd de la Chapelle, 75010 Paris, France.+lnstitute of Experimental Cardiology, USSR Cardiology Research Center, 3rd Cherepkovskaya Street 15A, Moscow 121552 USSR. To investigate the effect of chronic pressure overload on cardiac sarcoplasmic reticulum, we measured on crude tissue homogenates, the oxalate stimulated Ca2+ uptake, the level of Ca2+ dependent phosphorylated intermediate, the total amount of Ca2+ pumps (determined using a specific monoclonal antibody) and of the corresponding mRNA (using a rat heart Ca2+ ATPase cDNA). As compared to shams the Ca2+ uptake declined in mild and severe hypertrophy (from 12.1 * 1.2 nmoles Caz+/mg protein/min to 9.1 i 1.5 and 6.7 * 1 .l respectively ).The level of Ca2+ dependent phosphotylated intermediate is also depressed :from 69.7 It 8.2 in shams to 58.8 * 7.4 and 48.1 f 13.5 pmoles Plmg protein in mild and severe hypertrophy respectively. Using Sl nuclease mapping, we observed that the Ca2+ ATPase mRNA from sham-operated and hyperlrophied hearts were identical. Finally, the concentrations of Ca 2+ ATPase mRNA and protein in the left ventricle were unchanged in mild hypertrophy while in severe hypertrophy it decreased respectively to 68.7 ?I 12.9% and 80.1 f 15.5% of the amount measured in shams.The total amount of mRNA and enzyme per left ventricle was either unchanged or sliihtly increased. The stow velocity of relaxation of severely hypertrophied heart can be. at least partially, explained by the absence of an increase in the expression of the Ca 2* ATPase gene and by the relative diminution in the density of the Ca2* pumps. s.2