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Inhibition of myocyte hypertrophy by alpha-1 adrenergic blockade
J Mel
Cell
Cardiol21
(Supplement
271
ENERGETICS OF SARCOLEMMAL SODIUM MOVEMENTS DURING ISCHEMIA AND REPERFUSION IN THE NORMAL AND HYPERTHYROID RAT HEART. Kieran Clarke, Susan J. Kohler and Joanne S. Ingwall. NMR Laboratory for Physiological Chemistry, Brigham and Women’s Hospital, Boston, MA 02115 Cardiac hypertrophy induced by triiodothyronine (T3) is associated with an increase in Na+,K+ATPase activity (V,,,). We have previously shown that, compared to normal hearts, the hyperthyroid rat heart accumulates twice as much Na+ during 28 min total, global ischemia but extrudes it more to define the effectively during reperfusion. In the present study we have used 31P NMR spectroscopy changes in the high energy phosphate compounds that underlie these transsarcolemmal sodium Rats were given 7 daily injections of T3 (0.2 mg/kg, ip), after which their hearts were movements. removed and perfused with Krebs-Henseleit buffer at 100 mmHg constant pressure and 37OC. The amounts of CrP and ATP were lower in the hyperthyroid rat heart (67% and 20% resp.) and were depleted within the first 6 min of ischemia. In contrast, in the control hearts, ATP levels were still detectable after 26 min ischemia. Glycogen levels were -50% lower in the hyperthyroid rat hearts; thus less glycolytic ATP would have been produced in these hearts. Recovery of CrP and ATP was better in the hyperthyroid rat hearts. The more rapid loss of CrP and ATP in the hyperthyroid rat heart explains the greater increase in [Na+]i during ischemia, most likely due to greater inhibition of Na+,K+ATPase activity. In hyperthyroid hearts, the relatively higher levels of CrP and ATP during recovery, coupled with increased V,,,, explains why [Na+]i returns to pre-ischemic values. These results suggest that differences in Na+ influx and efflux can be explained by altered energetics.
272
INHIBITION T. Itagaki, Department Medicrne,
OF MYOCYTE Y. Toma. of Internal tibe, Japan.
II) (1989)
S.
HYPERTKOPHY Umemoto, Medicine,
BY ALPHA-~ S. Fukuta, Yamaguchi
ADRENERGIC R. Kusukawa. University
BLOCKAIJE. School
of
To determine the effect of alpha-l adrenergic blockade on myocyte (alpha-1 blocker) was administered to Wistar hypcrtrophy , bunazosin rats (n=23) after coronary artery ligation, using mini osmotic pump (0.2mg/day) for 4 weeks. Myocyte diameter was measured across nucleus in the noninfarcted nyocardium of the ventricular septum. Myocytc diameter of group with small infarcts (lZf2(mean~SU)~m) and group with large infarcts (14+2Dm) was significantly increased, compared to that of group without infarcts (IOflum). On the other hand, on bunazosin administration, myocyte diameter was 10+_2fium in group with small infarcts, i2?2,1?e in group with large infarcts, and lO?Ilom in group without infarcts. These data demonstrated the alpha-l blockade inhibited the hypertrophy of myocyte of groups with infarcts. Thus, myocyte hypertrophy is suggested to be mediated though alpha-1 receptor,
273
CARNITINE LIMITATION OF CARNITINE ACYLCARNITINE TRANSFERASE AND IMPAIRED LONG CHAIN FATTY ACID OXIDATION IN MECHANICALLY OVERLOADED RAT HEARTS. Z. El Alaoui-Talibi, J. Moravec. Laboratoire d’Energetique et de Cardiologie Cellulaire, INSERM, Faculte de Pharmacie, 21000 Dijon, France. The mechanically overloaded hearts exhibit often a decreased tissue content of the L-carnitine. In this work, rre tried to assess the impact of this latter alteration on their ability to oxidize long chain fatty acids. For this reason, the overall energy turnover (QOZ) and the 14CO2 production of control and volume overloaded rat hearts (3 month old aorto-caval fistule) perfused in vitro with the appropriate substrates have been compared. In volume overloaded hearts, both the oxygen consumption rate and the 141302 production were decreased to the same extent. At the same time, a progressive decline of LV performance could be detected. In contrast, the rate of oxygen consumption as well as the rate of 14CO2 production from 2.4 mM l-14C-octanoate were quite comparable to those of control hearts. Furthermore, the use of the exogenous octanoate prevented the mechanical failure of volume overloaded hearts. Our data suggest that the impaired exogenous long chain fatty acid oxidation resulted essentially from a substrate limitation of the mitochondrial carnitine acylcarnitine transferase. The other factors such as the concomitant oxidation of other substrate (glucose, unlabelled FFA) or a defect of 3oxidation per se seem to interfere to a lesser extent.
s.91
Cell
Cardiol21
(Supplement
271
ENERGETICS OF SARCOLEMMAL SODIUM MOVEMENTS DURING ISCHEMIA AND REPERFUSION IN THE NORMAL AND HYPERTHYROID RAT HEART. Kieran Clarke, Susan J. Kohler and Joanne S. Ingwall. NMR Laboratory for Physiological Chemistry, Brigham and Women’s Hospital, Boston, MA 02115 Cardiac hypertrophy induced by triiodothyronine (T3) is associated with an increase in Na+,K+ATPase activity (V,,,). We have previously shown that, compared to normal hearts, the hyperthyroid rat heart accumulates twice as much Na+ during 28 min total, global ischemia but extrudes it more to define the effectively during reperfusion. In the present study we have used 31P NMR spectroscopy changes in the high energy phosphate compounds that underlie these transsarcolemmal sodium Rats were given 7 daily injections of T3 (0.2 mg/kg, ip), after which their hearts were movements. removed and perfused with Krebs-Henseleit buffer at 100 mmHg constant pressure and 37OC. The amounts of CrP and ATP were lower in the hyperthyroid rat heart (67% and 20% resp.) and were depleted within the first 6 min of ischemia. In contrast, in the control hearts, ATP levels were still detectable after 26 min ischemia. Glycogen levels were -50% lower in the hyperthyroid rat hearts; thus less glycolytic ATP would have been produced in these hearts. Recovery of CrP and ATP was better in the hyperthyroid rat hearts. The more rapid loss of CrP and ATP in the hyperthyroid rat heart explains the greater increase in [Na+]i during ischemia, most likely due to greater inhibition of Na+,K+ATPase activity. In hyperthyroid hearts, the relatively higher levels of CrP and ATP during recovery, coupled with increased V,,,, explains why [Na+]i returns to pre-ischemic values. These results suggest that differences in Na+ influx and efflux can be explained by altered energetics.
272
INHIBITION T. Itagaki, Department Medicrne,
OF MYOCYTE Y. Toma. of Internal tibe, Japan.
II) (1989)
S.
HYPERTKOPHY Umemoto, Medicine,
BY ALPHA-~ S. Fukuta, Yamaguchi
ADRENERGIC R. Kusukawa. University
BLOCKAIJE. School
of
To determine the effect of alpha-l adrenergic blockade on myocyte (alpha-1 blocker) was administered to Wistar hypcrtrophy , bunazosin rats (n=23) after coronary artery ligation, using mini osmotic pump (0.2mg/day) for 4 weeks. Myocyte diameter was measured across nucleus in the noninfarcted nyocardium of the ventricular septum. Myocytc diameter of group with small infarcts (lZf2(mean~SU)~m) and group with large infarcts (14+2Dm) was significantly increased, compared to that of group without infarcts (IOflum). On the other hand, on bunazosin administration, myocyte diameter was 10+_2fium in group with small infarcts, i2?2,1?e in group with large infarcts, and lO?Ilom in group without infarcts. These data demonstrated the alpha-l blockade inhibited the hypertrophy of myocyte of groups with infarcts. Thus, myocyte hypertrophy is suggested to be mediated though alpha-1 receptor,
273
CARNITINE LIMITATION OF CARNITINE ACYLCARNITINE TRANSFERASE AND IMPAIRED LONG CHAIN FATTY ACID OXIDATION IN MECHANICALLY OVERLOADED RAT HEARTS. Z. El Alaoui-Talibi, J. Moravec. Laboratoire d’Energetique et de Cardiologie Cellulaire, INSERM, Faculte de Pharmacie, 21000 Dijon, France. The mechanically overloaded hearts exhibit often a decreased tissue content of the L-carnitine. In this work, rre tried to assess the impact of this latter alteration on their ability to oxidize long chain fatty acids. For this reason, the overall energy turnover (QOZ) and the 14CO2 production of control and volume overloaded rat hearts (3 month old aorto-caval fistule) perfused in vitro with the appropriate substrates have been compared. In volume overloaded hearts, both the oxygen consumption rate and the 141302 production were decreased to the same extent. At the same time, a progressive decline of LV performance could be detected. In contrast, the rate of oxygen consumption as well as the rate of 14CO2 production from 2.4 mM l-14C-octanoate were quite comparable to those of control hearts. Furthermore, the use of the exogenous octanoate prevented the mechanical failure of volume overloaded hearts. Our data suggest that the impaired exogenous long chain fatty acid oxidation resulted essentially from a substrate limitation of the mitochondrial carnitine acylcarnitine transferase. The other factors such as the concomitant oxidation of other substrate (glucose, unlabelled FFA) or a defect of 3oxidation per se seem to interfere to a lesser extent.
s.91