Cardiac function in spontaneously hypertensive diabetic rats

1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Working Heart ◽  
Diabetes Induction

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.

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.

Working heart function in diabetes is not improved by spironolactone treatment

2003 ◽  
Vol 81 (5) ◽  
pp. 493-496 ◽  
Author(s):  
Subodh Verma ◽  
Violet G Yuen ◽  
Mitesh Badiwala ◽  
Todd J Anderson ◽  
John H McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Potential Contribution ◽  
Receptor Blockade ◽  
Beneficial Effects ◽  
Aldosterone Receptor ◽  
Working Heart

Aldosterone antagonism has emerged as an important strategy for end-stage congestive heart failure. To evaluate the potential contribution of aldosterone towards the cardiac complications of diabetes, this study examined the effects of chronic aldosterone receptor blockade (with spironolactone) on isolated working heart function in streptozotocin (STZ) - induced diabetic rats. Wistar rats were divided into four groups: control, control spironolactone-treated, diabetic, and diabetic spironolactone-treated. Following chronic spironolactone treatment (8 weeks), cardiac function was assessed in terms of the rate of contraction (+dP/dT), rate of relaxation (–dP/dT), and left ventricular developed pressure (LVDP). Untreated diabetic rats exhibited marked cardiac dysfunction when compared with age matched controls (p < 0.001). Long-term spironolactone treatment did not improve these parameters. These data demonstrate the lack of beneficial effects of aldosterone receptor blockade on isolated working heart function in diabetes.Key words: aldosterone, streptozotocin-induced diabetes, aldosterone receptor blocker, spironolactone, cardiac function.

Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV)

1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill
Keyword(s):  
Blood Glucose ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Plasma Lipid ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Vanadium Complex ◽  
Significant Correction ◽  
Streptozotocin Diabetic Rats

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.

Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats

1999 ◽  
Vol 86 (3) ◽  
pp. 812-818 ◽  
Author(s):  
Kiminori Kato ◽  
Donald C. Chapman ◽  
Heinz Rupp ◽  
Anton Lukas ◽  
Naranjan S. Dhalla
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Binding Sites ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Carnitine Palmitoyltransferase ◽  
Heart Weight ◽  
High Affinity

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3′,-5-triiodo-l-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.

Anti-Apoptotic Effect of Magnolol in Myocardial Ischemia and Reperfusion Injury Requires Extracellular Signal-Regulated Kinase1/2 Pathways in Rat In Vivo

2008 ◽  
Vol 233 (10) ◽  
pp. 1280-1288 ◽  
Author(s):  
Yong Chun Jin ◽  
Kil Jung Kim ◽  
Young Min Kim ◽  
Yu Mi Ha ◽  
Hye Jung Kim ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Infarct Size ◽  
Function Analysis ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% ( P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury.

Hypertriglyceridemia in experimental diabetes: relationship to cardiac dysfunction

1994 ◽  
Vol 72 (5) ◽  
pp. 447-455 ◽  
Author(s):  
Brian Rodrigues ◽  
Paul F. Grassby ◽  
Mary L. Battell ◽  
Stephanie Y. N. Lee ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Plasma Triglyceride ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Of Increase

The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test die hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (±dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with die exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent die onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in die diabetic rat at this time point.Key words: diabetes, triglycerides, heart function, glucose oxidation.

Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats

1990 ◽  
Vol 68 (4) ◽  
pp. 514-518 ◽  
Author(s):  
Brian Rodrigues ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Insulin Dose ◽  
Cardiac Contractility ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Myosin Atpase ◽  
Bb Rat ◽  
Relaxation Rates ◽  
Bb Rats

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.Key words: diabetes, cardiac function, Wistar BB rat, myosin ATPase, cardiomyopathy.

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.

scholarly journals Sodium–glucose co‐transporter 2 inhibition with empagliflozin improves cardiac function in non‐diabetic rats with left ventricular dysfunction after myocardial infarction

2019 ◽  
Vol 21 (7) ◽  
pp. 862-873 ◽  
Author(s):  
Salva R. Yurista ◽  
Herman H.W. Silljé ◽  
Silke U. Oberdorf‐Maass ◽  
Elisabeth‐Maria Schouten ◽  
Mario G. Pavez Giani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular

Effects of forskolin on inotropic performance and phospholamban phosphorylation in exercise-trained hypertensive myocardium

2007 ◽  
Vol 102 (2) ◽  
pp. 628-633 ◽  
Author(s):  
Stephen C. Kolwicz ◽  
Hajime Kubo ◽  
Scott M. MacDonnell ◽  
Steven R. Houser ◽  
Joseph R. Libonati
Keyword(s):  
Heart Rate ◽  
Adenylyl Cyclase ◽  
Spontaneously Hypertensive Rat ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Chronic Hypertension ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Phospholamban Phosphorylation

β-Adrenergic receptor (β-AR) responsiveness is downregulated in left ventricular (LV) hypertrophy induced by chronic hypertension. While exercise training in hypertension enhances β-AR responsiveness, the role of adenylyl cyclase remains unclear. The purpose of the present study was to test whether treadmill running in the spontaneously hypertensive rat (SHR) model improves LV responsiveness to forskolin (FOR) or the combination of FOR + isoproterenol (FOR+ISO). Female SHR (16-wk) were randomly placed into sedentary (SHR-SED; n = 7) or treadmill-trained (SHR-TRD; n = 8) groups. Wistar-Kyoto (WKY; n = 7) animals acted as normotensive controls. Langendorff, isovolumic LV performance was established at baseline and during incremental FOR infusion (1 and 5 μmol/l) and FOR+ISO (5 μmol/l + 1×10−8 mol/l). Heart rate, systolic blood pressure, and heart-to-body weight ratio were lower in WKY relative to both SHR groups ( P < 0.05). LV performance and heart rate significantly increased in all groups to a similar extent with incremental FOR infusion. However, in the presence of 5 μmol/l FOR, ISO increased LV developed pressure, positive change in LV pressure, and negative change in LV pressure to a greater extent in SHR-TRD relative to SHR-SED ( P < 0.05). Phospholamban phosphorylation at the Thr17 was greater in SHR-TRD relative to SHR-SED and WKY ( P < 0.05). Absolute LV developed pressure was moderately correlated with phospholamban phosphorylation at both the Ser16 ( r = 0.64; P < 0.05) and Thr17 ( r = 0.52; P < 0.05). Our data suggest that the adenylyl cyclase step in the β-AR cascade is not downregulated in the early course of hypertension and that the enhanced β-AR responsiveness with training is likely mediated at levels other than adenylyl cyclase. Our data also suggest that β-AR inotropic responsiveness in the presence of direct adenylyl cyclase agonism is improved in trained compared with sedentary SHR hearts.

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