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Sodium-calcium exchange activity in hypertrophied rat heart vesicles
J Mol Cell Cardiol 21 (Supplement
III) (1989)
EXCHANGES IN p-ADRENERGIC RECEPTORS AND THE "SSUBUNIT OF GSPROTEIN IN HEARTS FROM PIGS WITH HYPERTHYROIDISM, VOLUME OVERLOAD AND AFTER CHRONIC DYNAMIC EXERCISE. H. Kirk Hammond, Lennart A. Ransnas, Jerene J. Waite, and Paul A. Insel. Departments of Pharmacology and Medicine, UCSD, and VAMC, La Jolla, CA, 92093 USA. We have initiated studies of cardiac hypertrophy in pigs using 3 models - thyroid hormone treatment, chronic dynamic exercise, and volume overload (aortocaval shunt) - and have examined ,9-adrenergic chronotropic response (EC.=,Ofor isoproterenol to increase heart rate), ,9-adrenergic receptors (using radioligand binding techniques), and levels of the as subunit of G, (by ELISA with an anti-peptide antibody and in some cases, by reconstitution in as-deficient membranes and measurement of us mRNA). Thyroid hormone treatment (5 1 mg/kg/d x 7 days) increased p-adrenergfc response, atria1 and left ventricular p-adrenergic receptor number (about P-fold) and amount ofo,(3-6 fold) assayed by both reconstitution and ELISA. Northern blot studies indicate little or no increase in a,mRNA at day 7 from hyperthyroid animals, thus suggesting post-transcriptional events By contrast, chronic dynamic exercise was associated in the change in level of asprotein. with a decrease in ,9-receptor number and an increase in p-adrenergic response and in as levels (by ELISA), while volume overload was associated with a decrease in p-adrenergic response, receptor number, and in preliminary studies inu,levels as well. These findings indicate that the pattern of changes in fl-adrenergic receptors and the asprotein are quite different in various forms of experimental cardiac hypertrophy; in general, changes in padrenergic response correlate better with levels of as than with p-receptor number.
2 9 SODlUM-CALCIUM EXCHANGE ACTMTY IN HYPERTROPHIED RAT HEART VESICLES. R. Hanf, I. Drubaix, I. BertrandBerrebi and L.G. Lelievre. INSERM U127 H6pital Lariboisi&e. Universitd Paris 7, 41 Bd de la Chapelle, 75010 Paris. Present adress : Hall des biotechnologies, Tour 54-64 5e &age, 2 place Jussieu, 75005 Paris. France. We show that the Na+/Ca2* exchange activity measured in sarcolemmal isolated vesicles of homogeneous orientation (inside-out) is decreased in membrane from pressure overload hypertrophied rat ventricles (H) when compared with vesicles from Sham-operated rat ventricles (S). The Na+-dependent-Ca2+ uptake as well as the Na+-dependent-Ca*+ efflux were depressed in exchange activity is altered in both reverse and membrane from H, suggesting that the Na+/Ca2+ forward mode (1.67M.48 v.s 2.77M.14 nmot/mg/2sec pcO.005 [Ca*+]o&ObM and 2.14rO.40 v.s 4.25r0.7 nrnoUmg/l0sec respectively). Such alteration seemed to be retated to a modification of the Ca*+ binding site since the apparent Km(Ca*+) for Na+-dependent-Ca*+ uptake was 10 fold higher in H than in S (I5.8kO.S v.s 1.15fl.58 PM). The Na+, which is known to compete with Ca*+ for the site A of the exchanger presented the same apparent affinity in H and S (Km(Na+)=lO+S mM v.s 12s mM respectively). The cellular basis of such modification is still unknown but might be related to defective regulation processes (phosphorylation, phospholipid However, these data have to be composition of the membrane bitayer, Ca 2+ dependent regulation...). compared to the peculiar Ca*+ metabolism and electrical properties of the cardiac myocyte hypertrophied by pressure overeload.
30
BETA-ADRENERGIC RECEPTORS VENTRICULAR AND ATRIALSUBTYPES DENSITY AND HEART RATE VARlABlLll-Y IN THYROTOXIC HYPERTROPHIED RAT HEARTS. H. Haouala’, L. Ollivier”, B. Chevalier**, P. Mansier”, B. Swynghedauw”, Ph. Coumel’. Department of Cardiology* and INSERM U127”, H6pital Lariboisidre, Paris, France. Evaluation of heart rate (HR) variability allows to study autonomic nervous system (ANS) changes at the sinus node level. Adult male rats were made thyrotoxic (T) by daily injections of 0.4 mg/kg of L-thyroxine. This resulted after 7 days in both ventricular (T= 697 of: 5 mg, n=12; control(C)= 541 f 4 mg, n-11, p
III) (1989)
EXCHANGES IN p-ADRENERGIC RECEPTORS AND THE "SSUBUNIT OF GSPROTEIN IN HEARTS FROM PIGS WITH HYPERTHYROIDISM, VOLUME OVERLOAD AND AFTER CHRONIC DYNAMIC EXERCISE. H. Kirk Hammond, Lennart A. Ransnas, Jerene J. Waite, and Paul A. Insel. Departments of Pharmacology and Medicine, UCSD, and VAMC, La Jolla, CA, 92093 USA. We have initiated studies of cardiac hypertrophy in pigs using 3 models - thyroid hormone treatment, chronic dynamic exercise, and volume overload (aortocaval shunt) - and have examined ,9-adrenergic chronotropic response (EC.=,Ofor isoproterenol to increase heart rate), ,9-adrenergic receptors (using radioligand binding techniques), and levels of the as subunit of G, (by ELISA with an anti-peptide antibody and in some cases, by reconstitution in as-deficient membranes and measurement of us mRNA). Thyroid hormone treatment (5 1 mg/kg/d x 7 days) increased p-adrenergfc response, atria1 and left ventricular p-adrenergic receptor number (about P-fold) and amount ofo,(3-6 fold) assayed by both reconstitution and ELISA. Northern blot studies indicate little or no increase in a,mRNA at day 7 from hyperthyroid animals, thus suggesting post-transcriptional events By contrast, chronic dynamic exercise was associated in the change in level of asprotein. with a decrease in ,9-receptor number and an increase in p-adrenergic response and in as levels (by ELISA), while volume overload was associated with a decrease in p-adrenergic response, receptor number, and in preliminary studies inu,levels as well. These findings indicate that the pattern of changes in fl-adrenergic receptors and the asprotein are quite different in various forms of experimental cardiac hypertrophy; in general, changes in padrenergic response correlate better with levels of as than with p-receptor number.
2 9 SODlUM-CALCIUM EXCHANGE ACTMTY IN HYPERTROPHIED RAT HEART VESICLES. R. Hanf, I. Drubaix, I. BertrandBerrebi and L.G. Lelievre. INSERM U127 H6pital Lariboisi&e. Universitd Paris 7, 41 Bd de la Chapelle, 75010 Paris. Present adress : Hall des biotechnologies, Tour 54-64 5e &age, 2 place Jussieu, 75005 Paris. France. We show that the Na+/Ca2* exchange activity measured in sarcolemmal isolated vesicles of homogeneous orientation (inside-out) is decreased in membrane from pressure overload hypertrophied rat ventricles (H) when compared with vesicles from Sham-operated rat ventricles (S). The Na+-dependent-Ca2+ uptake as well as the Na+-dependent-Ca*+ efflux were depressed in exchange activity is altered in both reverse and membrane from H, suggesting that the Na+/Ca2+ forward mode (1.67M.48 v.s 2.77M.14 nmot/mg/2sec pcO.005 [Ca*+]o&ObM and 2.14rO.40 v.s 4.25r0.7 nrnoUmg/l0sec respectively). Such alteration seemed to be retated to a modification of the Ca*+ binding site since the apparent Km(Ca*+) for Na+-dependent-Ca*+ uptake was 10 fold higher in H than in S (I5.8kO.S v.s 1.15fl.58 PM). The Na+, which is known to compete with Ca*+ for the site A of the exchanger presented the same apparent affinity in H and S (Km(Na+)=lO+S mM v.s 12s mM respectively). The cellular basis of such modification is still unknown but might be related to defective regulation processes (phosphorylation, phospholipid However, these data have to be composition of the membrane bitayer, Ca 2+ dependent regulation...). compared to the peculiar Ca*+ metabolism and electrical properties of the cardiac myocyte hypertrophied by pressure overeload.
30
BETA-ADRENERGIC RECEPTORS VENTRICULAR AND ATRIALSUBTYPES DENSITY AND HEART RATE VARlABlLll-Y IN THYROTOXIC HYPERTROPHIED RAT HEARTS. H. Haouala’, L. Ollivier”, B. Chevalier**, P. Mansier”, B. Swynghedauw”, Ph. Coumel’. Department of Cardiology* and INSERM U127”, H6pital Lariboisidre, Paris, France. Evaluation of heart rate (HR) variability allows to study autonomic nervous system (ANS) changes at the sinus node level. Adult male rats were made thyrotoxic (T) by daily injections of 0.4 mg/kg of L-thyroxine. This resulted after 7 days in both ventricular (T= 697 of: 5 mg, n=12; control(C)= 541 f 4 mg, n-11, p