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Effect of diabetes and selenite on contractile responses and β-adrenergic signaling in rat hearts
THE EFFECT OF OXIDATIVE STRESS ON Na’K’ ATPASE ISOFORM EXPRESSION IN RAT HEART DURING ISCHEMIA-REPERFUSION Petr Ostadal, Adel B. Elmoselhi, lrena Zdobnicka, Donald Chapman, Mona Chappellaz 8 Naranjan S. Dhalla. Inst. of Cardiovasc. Sciences, SBGH Research Centre, and Dept of Physiology, Faculty of Medicine, University of Manltoba, Winnlpeg, Manitoba, Canada Dept of Internal Medicine, University Hospital Motol, Prague, Czech Republic The aim of this study was to assess (a) whether depression of cardiac performance and Na’-K’-ATPase actlvtty during lschemla (30 mln) and reperfuslon (60 mln) (I/Rj IS associated with alteration In Na’-K’-ATPase lsoform and fb) whether expresslon oxldatlve stress (0s) partlclpates in this alteratton lsoform protein and mRNA contents were studled In Isolated rat hearts subjected to l/R 1’) the presence or absence of superoxide dlsmutase plus catalase (SOD+CAT) The effect of I/R was compared tc H;Oz or xanthlne pigs xanthlne oxldase (Xx0) treatment The 0; CI~ and B., C, p3 lsoforms were s:gnlflcantly depressed by I/R H202 and XX0 on both protelr: and mRNA leveis the effect of I/R was blocked by SOD+CAT I/R-Induced reduction of a, was less and was not protectec by antIoxIdants H202 and XX0 depressed a, mRNA but not protein content These results lndlcate that I/R causes alteration in Na’-K’-ATPase isoform expresslon and that OS plays a role In this alteration AntIoxIdant treatment Improves expression of a!l soforms except a:, which appears to be more resIstant to OS
PROTECTION OF NEONATAL RAT HEART: ISCHEMIC PRECONDITIONING AND CHRONIC HYPOXIA I. 0939dalov& B. OSt’gdal, & F. KolM. Inst Physiol, Acad Sci, Center Exp Cardiovasc Res, Prague, Czech Republic. Protectwe effect of mtemuttent lugh altitude (THA) hypoxia and/or ~shrn~c prcodhoning (P) and the mle of mno KATP channels andNOmthepmtechonwasanaIyzedinneonatalratbcart.Hearts ~sdat~~Ia&ys 1,4,7and IO wereperl&d(Langendor@\nth Krebs-Henselat solution at constant pressure, temperature and mmulahon rate. Gmtriactile fimctlon was d by an isometric
forcebansdwr.IPwasmdwedbyduw3-mmperiodsofglokal ~schemia, each separated by 5-mm pencds of qerfuwm. Prenatal hypoxia WBSinduced by exposure of mok to IHA @arc&amber. 8 May. 5000 m) fk day I5 to 20 of pregnancy, postt~& hypoxia by sucklings l?om wtal day 1 to 6 and 9. &natal exposure failed to improve ~schermc tolerance on day 1, but postnatal exposure improved recovery of developed force on day 7 (336 vs. 43*40/o), and IO (3w vs. 54G%). Cmbmam of MA and IP mlucecl higher ptechve effect in all age groups, vrcluding postnatal day I (48ti vs. 56z3%). Neiti nut0 KAp channel blocker, 5-
hydmxyckmoate nor the NOS ml&itor LNAME &d abohsh protection by IP m cuntrols but they decreased protection by IHA hypoxia. The protective effect of IP m hypoxic animals was, however, presewed. It seems likely that mitoKA,&mnels and NO rMy he invokd in tk protective rncxhamsmsof adaptation to MA but not of that of IP. at least in neonates. Grant No. 3051OOi1659,Chant Agency oftk Czech Repubhc.
Do docosakutnoic acid and Trimetadiw inthem tbe mItmbodd mpiration cardiac 6ben in type I model of diabetes ? Stephanie Ovide-Bordeaux, Bescond-Jacquet+, Alain Ch%tenay-Malabry, France;
of
Gcile HCliits-Toussaint, Anne Grynberg. INRA-LMFCV, * IRIS, Courbevoie, France.
In the diabetic heart, the part of fatty acid (FA) @oxidation in ATP production increases, and alterations of membrane lipid composition play a key role in these metabolic changes. We studied the effect of a change in phospholipid turnover (TMZ, 7.5 mgd’), or FA composition (DHA, 200 mitochondrial respiration in mg.d-‘), on saponinpermeabilized cardiac fibers in the streptozotocin model of type I diabetes. In the presence of glutamate or pyruvate + malate, neither diabetes nor treatment changed the respiration with or without ADP 2 mM and creatine 20 mM. The apparent K, for ADP (with creatine 20 mM) in diabetics fibers (222.9i48.5 pM vs increased 105.2ztl4.5 PM), but both TMZ and DHA prevented this alteration. Diabetes inhibited the respiration stimulated by ADP I mM (Vmax) with both octanoate (14.03ki.40 v.5 17.141t3.42 l.~moles 02.min-‘.g-‘) and palmitoylcamitint (PC) (9.84ti.94 vs ll.71~.99 pmoles 02.min.‘.g-‘). but neither DHA nor TMZ influenced this effect. llowever in the presence of PC, TMZ limited the increase of ACR (Vmax/Vo) : 4.04 -+ 0.43 vs 5.45 f 0.53 In conclusion, diabetes impairs the affinity of mitochondria for ADP, but this effect can he attenuated by DHA or TMZ. This metabolic changes may be related to mitochondrial membrane lipid alterations, since they could be improved by treatments affecting membrane homeostasis.
EFFECT OF DIABETES AND SELENITE ON CONTRACTILE RESPONSES AND f5ADRENERGIC SIGNALING IN RAT HEARTS Semir ozdemir, Murat Ayaz, Ozlem Ugur. Belma Turan Ankara University, Medical Faculty, and Dept Pharm. and Clin. Pharm.,
Ugur, Dept.
Mehmet Biophysics
TURKEY
We investigated the effect of STZ-induced diabetes and selenite (SE) treatment on the responses of isolated rat hearts to P-adrenergic receptor (P-AR) sfimulation by isoproterenol (ISO). Basal and ISOinduced max tension, rates of tension development (+dT/dt) and relaxation (-dT/dt) were masured in isolated hearts from control, diabetic, SE-treated control and diabetic rats. The max of developed tensions of basal contractions were similar in all groups, but IS0 responses, when compared to control, were smaller (about o/015) in all treatsd groups. Baseline +dT/dt and -dT/dt were decreased in
diabetes and Se-treatment did not alter these parameters In diabetic group. IS0 induced a similar increase in +dT/dt in all groups, but IS0 induced increase in -dT/dt was higher in diabetics and SEtreated diabetics. Heart rate was found to be slower in both diabetic groups. Our preliminary results suggest that there may be a small but significant increase in IjAR density and P-AR-Gs coupling in diabetic hearts which is not affected by SE treatment * .Illl\ \rMi
wa9 suppoRed h\
.\,‘Kb
2~1lJl-oX494hl
and 1111 WK.I2OlYI
PROTECTION OF NEONATAL RAT HEART: ISCHEMIC PRECONDITIONING AND CHRONIC HYPOXIA I. 0939dalov& B. OSt’gdal, & F. KolM. Inst Physiol, Acad Sci, Center Exp Cardiovasc Res, Prague, Czech Republic. Protectwe effect of mtemuttent lugh altitude (THA) hypoxia and/or ~shrn~c prcodhoning (P) and the mle of mno KATP channels andNOmthepmtechonwasanaIyzedinneonatalratbcart.Hearts ~sdat~~Ia&ys 1,4,7and IO wereperl&d(Langendor@\nth Krebs-Henselat solution at constant pressure, temperature and mmulahon rate. Gmtriactile fimctlon was d by an isometric
forcebansdwr.IPwasmdwedbyduw3-mmperiodsofglokal ~schemia, each separated by 5-mm pencds of qerfuwm. Prenatal hypoxia WBSinduced by exposure of mok to IHA @arc&amber. 8 May. 5000 m) fk day I5 to 20 of pregnancy, postt~& hypoxia by sucklings l?om wtal day 1 to 6 and 9. &natal exposure failed to improve ~schermc tolerance on day 1, but postnatal exposure improved recovery of developed force on day 7 (336 vs. 43*40/o), and IO (3w vs. 54G%). Cmbmam of MA and IP mlucecl higher ptechve effect in all age groups, vrcluding postnatal day I (48ti vs. 56z3%). Neiti nut0 KAp channel blocker, 5-
hydmxyckmoate nor the NOS ml&itor LNAME &d abohsh protection by IP m cuntrols but they decreased protection by IHA hypoxia. The protective effect of IP m hypoxic animals was, however, presewed. It seems likely that mitoKA,&mnels and NO rMy he invokd in tk protective rncxhamsmsof adaptation to MA but not of that of IP. at least in neonates. Grant No. 3051OOi1659,Chant Agency oftk Czech Repubhc.
Do docosakutnoic acid and Trimetadiw inthem tbe mItmbodd mpiration cardiac 6ben in type I model of diabetes ? Stephanie Ovide-Bordeaux, Bescond-Jacquet+, Alain Ch%tenay-Malabry, France;
of
Gcile HCliits-Toussaint, Anne Grynberg. INRA-LMFCV, * IRIS, Courbevoie, France.
In the diabetic heart, the part of fatty acid (FA) @oxidation in ATP production increases, and alterations of membrane lipid composition play a key role in these metabolic changes. We studied the effect of a change in phospholipid turnover (TMZ, 7.5 mgd’), or FA composition (DHA, 200 mitochondrial respiration in mg.d-‘), on saponinpermeabilized cardiac fibers in the streptozotocin model of type I diabetes. In the presence of glutamate or pyruvate + malate, neither diabetes nor treatment changed the respiration with or without ADP 2 mM and creatine 20 mM. The apparent K, for ADP (with creatine 20 mM) in diabetics fibers (222.9i48.5 pM vs increased 105.2ztl4.5 PM), but both TMZ and DHA prevented this alteration. Diabetes inhibited the respiration stimulated by ADP I mM (Vmax) with both octanoate (14.03ki.40 v.5 17.141t3.42 l.~moles 02.min-‘.g-‘) and palmitoylcamitint (PC) (9.84ti.94 vs ll.71~.99 pmoles 02.min.‘.g-‘). but neither DHA nor TMZ influenced this effect. llowever in the presence of PC, TMZ limited the increase of ACR (Vmax/Vo) : 4.04 -+ 0.43 vs 5.45 f 0.53 In conclusion, diabetes impairs the affinity of mitochondria for ADP, but this effect can he attenuated by DHA or TMZ. This metabolic changes may be related to mitochondrial membrane lipid alterations, since they could be improved by treatments affecting membrane homeostasis.
EFFECT OF DIABETES AND SELENITE ON CONTRACTILE RESPONSES AND f5ADRENERGIC SIGNALING IN RAT HEARTS Semir ozdemir, Murat Ayaz, Ozlem Ugur. Belma Turan Ankara University, Medical Faculty, and Dept Pharm. and Clin. Pharm.,
Ugur, Dept.
Mehmet Biophysics
TURKEY
We investigated the effect of STZ-induced diabetes and selenite (SE) treatment on the responses of isolated rat hearts to P-adrenergic receptor (P-AR) sfimulation by isoproterenol (ISO). Basal and ISOinduced max tension, rates of tension development (+dT/dt) and relaxation (-dT/dt) were masured in isolated hearts from control, diabetic, SE-treated control and diabetic rats. The max of developed tensions of basal contractions were similar in all groups, but IS0 responses, when compared to control, were smaller (about o/015) in all treatsd groups. Baseline +dT/dt and -dT/dt were decreased in
diabetes and Se-treatment did not alter these parameters In diabetic group. IS0 induced a similar increase in +dT/dt in all groups, but IS0 induced increase in -dT/dt was higher in diabetics and SEtreated diabetics. Heart rate was found to be slower in both diabetic groups. Our preliminary results suggest that there may be a small but significant increase in IjAR density and P-AR-Gs coupling in diabetic hearts which is not affected by SE treatment * .Illl\ \rMi
wa9 suppoRed h\
.\,‘Kb
2~1lJl-oX494hl
and 1111 WK.I2OlYI