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Calcium channels in normal and hypertrophied rat heart
J Mol Cell Cardiol 21 (Supplement
III) (1989)
49 CALCIUMCHANNELS IN NORMAL AND HYPERTROPHIED RAT HEART. E. Mayoux. F. Scamps*, P. Oliviem, G. Vassort*. D. Charlemagne. INSERM U-127. Hopital LatiboisiCn. 75010 Paris and *INSERM U-241. Universite Paris-Sud 91405 &say. FRANCE. The lenghtening in action potential duration observed in hypcnrophied heart might be related to changes in ionic transport acrossthe samolemma. The number of calcium channels measured by 3HPN200-1 10 binding to sarcolemmaf fraction, the dissociation constant and the dissociation rate constant were unchanged in hypertmphied rat heart ‘tbc ICa amplitude anafysed by the whole-cell patch clamp was higher in hypertmphicd However, no significant difference was observed in current density (6.3 and 5.9 pA/pF
than in normal myocytes. in hypertmphied and normal cells rwpectively) as well asvoltage and time dependance.The increase in ICa amplitude induced by isopmnaline was less marked in hypertmphied heart altbought the sensitivityof ICa to isopmnahne was not modified. ‘Ihe results show that in hypertmphied left ventricle, the total number of calcium channels was increased in parallel with the hypertmphy. Moreover, the increased surface area of the hypenrophied myocytes indicate that the density of the calcium cbsnncfs and the inftw. of calcium per unit volume am maintained. ‘he decrease stimulation of ICa by Badrenergic agonist well agree with the reduced number of B-receptors. ‘Ihese might be adaptadonal pmcessesto pressure overload.
50
ATRIAL NATRIURETIC FACTOR GENE ACTIVATION IN RAT LEFT VENTRICLE : ROLE OF VENTRICULAR FILLING PRESSURE. J.J. Mercadier, J.B. Michel’, MA. Zongazo”, D. de la Bastie, C. Wisnewsky, B. Levy”‘, K. Schwartz. INSERM Unite 127, ‘36, “‘141 and “Dpt of Biochemistry, CHU Pit& salpetriere. Paris, France. We have previously reported that the accumulation of the messenger ribonucleic acid (mRNA) coding for the Atrial Natriuretic Factor (ANF) observed in the rat left ventricle (LV) following coarctation of the abdominal aorta, peaks at day 4, long before stable hypertension and LV hypertrophy. In order to characterize some of the possible mechanisms responsible for this accumulation, we determined in male Wistar rats (250 g) sacrified 4 or 30 days following coarctation, LV end diastolic pressure (LVEDP), plasma renin (PRC) and plasma ANF (pl. ANF) concentrations. ANF mRNA concentration, LVEDP and PRC were markedly increased as compared to controls at day 4, when aortic pressures were still normal and in the absence of significant LV hypertrophy. By contrast at day 30. during stable hypertension and LV hypertrophy. both LVEDP and PRC returned to control values whereas pl. ANFwas increased and LV-ANF mkNA was about half that observed at day 4. Our data show that ventricular ANF gene expression following coarctation of the abdominal aorta in the rat is a multifactorial phenomenon that does not only depends upon hypertension and hypertrophy and that ventricular distension resulting from an increase in LVEDP is likely a powerfull trigger for this activation, at least during the early stages.
5 1 ATRIAL NATRIURETIC FACTOR GENE EXPRESSION IN THE HUMAN HEART DURING ONTOGENIC DEVELOPMENT. J.J. Mercadier, M.A. Zongaro’, G. Buttler-Brown”, D. Gras”‘, A. Carayon’, K. Schwartz. INSERM Unite 127, H8oital Lariboisere. ‘CHU Pitie-Salp&riere. l *lNSERM Unite 262, d’Aix-Marseille II, France. H8pital Baudelocque, Paris, “‘Unfversite Developmental regulation of Atrial Natriuretic Factor (ANF) production by atria and ventricles has been particularly well studied in rats, but little is known about the ontogenesis of myocardial ANF production in man, except that in utero, the ventricular concentrations of immunoactive ANF (IR ANF) are high. We have investigated the level of expression of the ANF gene in the human heart during ontogenic development by determining the concentrations of ANF messenger ribonucleic acid (mRNA), of IR ANF and of receptor reactive ANF (RR ANF), in myocardial samples of the various heart chambers. Ventricular ANF mRNA concentration was hfgh in utero, as early as the 13th week of gestation. At 29 weeks, it was almost identical in the left and right ventricles, averaging 50 times the corresponding adult levels. A two fold decrease was observed at the time of delivery, followed by a rapid decrease towards the low adult levels after birth, with a more rapid decrease in the right than in the left ventricle. The concentrations of IR ANF and RR ANF in utero were higher than the corresponding adult concentrations, but this increase was only moderate as compared to that of ANF mRNA. Thus, the expression of the ANF gene in the human ventricle progressively decreases during ontogenic development. By contrast, its expression in the atria is only little affected. S.18
III) (1989)
49 CALCIUMCHANNELS IN NORMAL AND HYPERTROPHIED RAT HEART. E. Mayoux. F. Scamps*, P. Oliviem, G. Vassort*. D. Charlemagne. INSERM U-127. Hopital LatiboisiCn. 75010 Paris and *INSERM U-241. Universite Paris-Sud 91405 &say. FRANCE. The lenghtening in action potential duration observed in hypcnrophied heart might be related to changes in ionic transport acrossthe samolemma. The number of calcium channels measured by 3HPN200-1 10 binding to sarcolemmaf fraction, the dissociation constant and the dissociation rate constant were unchanged in hypertmphied rat heart ‘tbc ICa amplitude anafysed by the whole-cell patch clamp was higher in hypertmphicd However, no significant difference was observed in current density (6.3 and 5.9 pA/pF
than in normal myocytes. in hypertmphied and normal cells rwpectively) as well asvoltage and time dependance.The increase in ICa amplitude induced by isopmnaline was less marked in hypertmphied heart altbought the sensitivityof ICa to isopmnahne was not modified. ‘Ihe results show that in hypertmphied left ventricle, the total number of calcium channels was increased in parallel with the hypertmphy. Moreover, the increased surface area of the hypenrophied myocytes indicate that the density of the calcium cbsnncfs and the inftw. of calcium per unit volume am maintained. ‘he decrease stimulation of ICa by Badrenergic agonist well agree with the reduced number of B-receptors. ‘Ihese might be adaptadonal pmcessesto pressure overload.
50
ATRIAL NATRIURETIC FACTOR GENE ACTIVATION IN RAT LEFT VENTRICLE : ROLE OF VENTRICULAR FILLING PRESSURE. J.J. Mercadier, J.B. Michel’, MA. Zongazo”, D. de la Bastie, C. Wisnewsky, B. Levy”‘, K. Schwartz. INSERM Unite 127, ‘36, “‘141 and “Dpt of Biochemistry, CHU Pit& salpetriere. Paris, France. We have previously reported that the accumulation of the messenger ribonucleic acid (mRNA) coding for the Atrial Natriuretic Factor (ANF) observed in the rat left ventricle (LV) following coarctation of the abdominal aorta, peaks at day 4, long before stable hypertension and LV hypertrophy. In order to characterize some of the possible mechanisms responsible for this accumulation, we determined in male Wistar rats (250 g) sacrified 4 or 30 days following coarctation, LV end diastolic pressure (LVEDP), plasma renin (PRC) and plasma ANF (pl. ANF) concentrations. ANF mRNA concentration, LVEDP and PRC were markedly increased as compared to controls at day 4, when aortic pressures were still normal and in the absence of significant LV hypertrophy. By contrast at day 30. during stable hypertension and LV hypertrophy. both LVEDP and PRC returned to control values whereas pl. ANFwas increased and LV-ANF mkNA was about half that observed at day 4. Our data show that ventricular ANF gene expression following coarctation of the abdominal aorta in the rat is a multifactorial phenomenon that does not only depends upon hypertension and hypertrophy and that ventricular distension resulting from an increase in LVEDP is likely a powerfull trigger for this activation, at least during the early stages.
5 1 ATRIAL NATRIURETIC FACTOR GENE EXPRESSION IN THE HUMAN HEART DURING ONTOGENIC DEVELOPMENT. J.J. Mercadier, M.A. Zongaro’, G. Buttler-Brown”, D. Gras”‘, A. Carayon’, K. Schwartz. INSERM Unite 127, H8oital Lariboisere. ‘CHU Pitie-Salp&riere. l *lNSERM Unite 262, d’Aix-Marseille II, France. H8pital Baudelocque, Paris, “‘Unfversite Developmental regulation of Atrial Natriuretic Factor (ANF) production by atria and ventricles has been particularly well studied in rats, but little is known about the ontogenesis of myocardial ANF production in man, except that in utero, the ventricular concentrations of immunoactive ANF (IR ANF) are high. We have investigated the level of expression of the ANF gene in the human heart during ontogenic development by determining the concentrations of ANF messenger ribonucleic acid (mRNA), of IR ANF and of receptor reactive ANF (RR ANF), in myocardial samples of the various heart chambers. Ventricular ANF mRNA concentration was hfgh in utero, as early as the 13th week of gestation. At 29 weeks, it was almost identical in the left and right ventricles, averaging 50 times the corresponding adult levels. A two fold decrease was observed at the time of delivery, followed by a rapid decrease towards the low adult levels after birth, with a more rapid decrease in the right than in the left ventricle. The concentrations of IR ANF and RR ANF in utero were higher than the corresponding adult concentrations, but this increase was only moderate as compared to that of ANF mRNA. Thus, the expression of the ANF gene in the human ventricle progressively decreases during ontogenic development. By contrast, its expression in the atria is only little affected. S.18