The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines

1983 ◽  
Vol 61 (5) ◽  
pp. 439-448 ◽  
Author(s):  
Gary D. Lopaschuk ◽  
Sidney Katz ◽  
John H. McNeill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Heart Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Microsomal Preparation ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Gradual Onset ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
Long Chain

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2–5.0 μM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62–73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations < 7 μM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.

Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats

1983 ◽  
Vol 245 (6) ◽  
pp. H969-H976 ◽  
Author(s):  
G. D. Lopaschuk ◽  
A. G. Tahiliani ◽  
R. V. Vadlamudi ◽  
S. Katz ◽  
J. H. McNeill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Transport ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Heart Apparatus

Cardiac sarcoplasmic reticulum (SR) function and SR levels of long-chain (LC) acylcarnitines were determined in streptozotocin-induced diabetic rats treated with insulin or D,L-carnitine. ATP-dependent calcium transport was significantly depressed in cardiac SR isolated from untreated diabetic rats compared with control rats. Diabetic rat cardiac SR levels of LC acylcarnitines were also significantly elevated. Various parameters of heart function (left ventricular developed pressure, +dP/dT, and -dP/dT), as determined on an isolated working heart apparatus, were found to be depressed in untreated diabetic rats. Cardiac SR isolated from diabetic rats treated throughout the study period with insulin or D,L-carnitine did not have elevated levels of LC acylcarnitines associated with SR membrane nor was SR calcium transport activity depressed. Heart function in the diabetic rats treated with insulin was similar to control rat hearts but heart function remained depressed in diabetic rats treated with D,L-carnitine. The data suggest that the LC acylcarnitines are involved in the observed impairment of cardiac SR function in diabetic rats. Other factors, however, must be contributing to the depression in heart function noted in these animals.

The effect of chronic alloxan- and streptozotocin-induced diabetes on isolated rat heart performance

1982 ◽  
Vol 60 (7) ◽  
pp. 902-911 ◽  
Author(s):  
Rao V. S. V. Vadlamudi ◽  
Robert L. Rodgers ◽  
John H. McNeill
Keyword(s):  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Cardiac Performance ◽  
Diabetic Rat ◽  
Heart Performance ◽  
Rat Hearts ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes

Cardiac disease is a common secondary complication appearing in chronic diabetics. Isolated perfused working hearts obtained from both acute and chronic diabetic rats have also been shown to exhibit cardiac functional abnormalities when exposed to high work loads. We studied cardiac performance at various time points after induction of diabetes in rats to determine exactly when functional alterations appeared and whether these alterations progressed with the disease state. Female Wistar rats were made diabetic by a single i.v. injection of either alloxan (65 mg/kg) or streptozotocin (STZ 60 mg/kg). Cardiac performance was assessed at 7, 30, 100, 180, 240, and 360 days after induction of diabetes using the isolated perfused working heart technique. No changes were observed in the positive and negative dP/dt development at various atrial filling pressures in the diabetic hearts 7 days after treatment. Alloxan diabetic rat hearts exhibited depressed left ventricular pressure and positive and negative dP/dt development when perfused at high atrial filling pressures, at 30. 100, and 240 days after treatment. STZ diabetic rat hearts exhibited depressed cardiac performance at high atrial filling pressures at 100, 180, and 360 days after treatment, but not at 30 days after treatment. Control hearts exhibited slight but significant depressions in cardiac function with age. These results suggest that cardiac functional alterations appear in diabetic rats about 30 days after induction and progress with the disease. These alterations may indicate the development of a cardiomyopathy.

Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry

1984 ◽  
Vol 62 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Chain Acyl ◽  
Uptake Activity ◽  
Streptozotocin Diabetic Rats ◽  
Developed Pressure

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

scholarly journals The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats

2017 ◽  
Vol 95 (11) ◽  
pp. 1343-1350
Author(s):  
Aleksandra Vranic ◽  
Stefan Simovic ◽  
Petar Ristic ◽  
Tamara Nikolic ◽  
Isidora Stojic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systolic Function ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Albino Rats ◽  
Acute Administration ◽  
Rat Hearts ◽  
Patients With Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Wistar Albino Rats

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Biochemical Basis of Heart Function. IV. Energy Metabolism and Calcium Transport in Hearts of Vitamin E Deficient Rats

1971 ◽  
Vol 49 (10) ◽  
pp. 909-918 ◽  
Author(s):  
Margaret Fedelesova ◽  
Prakash V. Sulakhe ◽  
John C. Yates ◽  
Naranjan S. Dhalla
Keyword(s):  
Vitamin E ◽  
Sarcoplasmic Reticulum ◽  
Heart Function ◽  
Adenine Nucleotides ◽  
Creatine Phosphate ◽  
Normal Diet ◽  
Vitamin E Deficiency ◽  
Deficient Diet ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Biochemical Basis

Feeding a vitamin E deficient diet to rats for 10 weeks was found to decrease myocardial creatine phosphate, ATP, ATP/ADP ratio, NAD+, NADP+, and NADPH, whereas the level of ADP was increased without any changes in the levels of AMP, total adenine nucleotides, NADH, and ATP/AMP ratio. The levels of ATP and pyridine nucleotides were restored fully, whereas creatine phosphate was restored partially on feeding a normal diet for 4 weeks to animals previously on the vitamin E deficient diet for 10 weeks. Vitamin E deficiency was found to increase cardiac lactate, pyruvate, and lactate/pyruvate ratio and decrease the activities of lactate dehydrogenase and malate dehydrogenase. The activity of Na+–K+-stimulated, ouabain-sensitive ATPase was markedly elevated in the hearts of animals on the vitamin E deficient diet. The ATP-dependent calcium accumulation by the sarcoplasmic reticular fraction in the absence and presence of P1 or oxalate was greater in the vitamin E deficient heart. Vitamin E deficiency also increased the Ca2+-stimulated ATPase activity of the cardiac sarcoplasmic reticulum. Although myocardial contractility of the hearts from vitamin E deficient rats was depressed, no damage to the ultrastructures of mitochondria and sarcoplasmic reticulum was apparent. These results indicate marked alterations in myocardial metabolism due to vitamin E deficiency and it is suggested that such changes are due to abnormalities in the processes of both energy production and utilization.

Calcium handling by sarcoplasmic reticulum of neonatal swine cardiac myocytes

1997 ◽  
Vol 273 (1) ◽  
pp. H192-H199
Author(s):  
C. M. Hohl ◽  
B. Livingston ◽  
J. Hensley ◽  
R. A. Altschuld
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ventricular Myocytes ◽  
Heart Function ◽  
Binding Capacity ◽  
Calcium Handling ◽  
Maximal Effect ◽  
Binding Studies ◽  
Human Infants ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Length Changes

In recent years, because of similarities to human infants, neonatal piglets have increasingly become the model of choice for studying neonatal heart function. However, the cardiac sarcoplasmic reticulum (SR) has not been thoroughly characterized in this species. Accordingly, Ca2+ pump kinetics, efflux channel characteristics, Ca2+ transients, and contractile movements were examined in isolated newborn piglet cardiac ventricular myocytes. Maximum uptake rate (Vmax) and concentration required to produce a half-maximal effect (K0.5) for oxalate-supported, ATP-dependent 45Ca2+ uptake by the SR of digitonin-lysed myocytes were 285 +/- 17 nmol 45Ca2+.min-1.mg-1 and 0.69 +/- 0.07 microM, respectively. In the absence of phospholamban phosphorylation, Vmax was reduced to 195 +/- 26 nmol 45Ca2+.min-1.mg-1 (P < 0.05 vs. control) and K0.5 increased to 1.28 +/- 0.13 microM (P < 0.05 vs. control). [3H]ryanodine binding studies yielded a maximum binding capacity of 181 +/- 12 fmol/mg and a dissociation constant of 1.7 +/- 0.2 nM. Raising extracellular Ca2+ (0.5-5 mM) increased peak amplitude and decreased the duration of electrically stimulated fura 2 Ca2+ transients and recordings of cell length changes. Both ryanodine and 2,5-di-tert-butylhydroquinone, an inhibitor of SR calcium adenosinetriphosphatase, completely abolished Ca2+ transients in piglet myocytes. These studies indicate that the SR has a significant role in excitation-contraction coupling in neonatal piglet myocytes.

Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium

2004 ◽  
Vol 101 (5) ◽  
pp. 1145-1152 ◽  
Author(s):  
Julien Amour ◽  
Jean-Stéphane David ◽  
Benoît Vivien ◽  
Pierre Coriat ◽  
Bruno Riou
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Alpha Adrenoceptor ◽  
Positive Inotropic Effects

Background Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. Results Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P &lt; 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P &lt; 0.05) and sevoflurane (161 +/- 40%; P &lt; 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.

Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats

2006 ◽  
Vol 84 (5) ◽  
pp. 728-736 ◽  
Author(s):  
V. Gopalakrishnan ◽  
J. Arunakaran ◽  
M. M. Aruldhas ◽  
N. Srinivasan
Keyword(s):  
Diabetes Mellitus ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Diabetic Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Adult Rats ◽  
Trap Activity ◽  
Female Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
Turnover Markers

Diabetes mellitus and estrogen deficit are known causes of osteopenia in animal models as well as in humans. In the present work, the combined effect of ovariectomy and diabetes was investigated. Diabetes was induced in ovary-intact and ovariectomized female Wistar rats with a single injection (50 mg/kg body weight, i.p.) of streptozotocin. The rats were administered insulin (I) daily or 17-β estradiol (E2) on alternate days for a period of 35 days and sacrificed. Serum calcium (Ca2+), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), vertebral ALP, collagen, and glycosaminoglycans were estimated. The levels of serum Ca2+and P increased in diabetic rats, but decreased after I or E2treatments. Serum ALP and TRAP activity increased in the ovary-intact and ovariectomized diabetic rats. Vertebral ALP activity increased in ovariectomized diabetic rats, but decreased in diabetic rats, which were treated with I or E2. In the vertebrae, TRAP activity was elevated as a result of diabetes, but this was prevented by insulin or estradiol. Diabetes induced a decrease in total collagen in the vertebrae, while I or E2treatment induced an increase. The levels of chondroitin sulphate and heparan sulphate decreased significantly in the vertebrae of both ovary-intact and ovariectomized diabetic rats, while hyaluronic acid increased. In conclusion, diabetes and ovariectomy each seem to affect the process of matrix formation and mineralization in the bone, and this is aggravated by the combination of diabetes and ovariectomy. The effects of I and E2were similar, and both hormones reversed the changes brought about by diabetes.

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