Modulation of hydrogen sulfide synthesis improve heart function and endothelium-dependent vasorelaxation in diabetes

Author(s):  
Natalya A. Dorofeyeva ◽  
Iulia P. Korkach ◽  
Olena E. Kutsyk ◽  
Vadim Sagach

Abstract Diabetes dramatically increases the risk of cardiovascular complications. The endothelial dysfunction and diastolic heart dysfunction are associated with a decreasing level of hydrogen sulfide (H2S) and inhibition of the activity of endothelial NO-synthase in diabetes. The aim of work is to investigate the effect of modulation of hydrogen sulfide synthesis on heart functions and vasorelaxation in diabetes. The DL-propargylglycine and L-cysteine were administered intraperitoneally. H2S content in the heart tissue, markers of oxidative stress, iNOS and cNOS activities, endothelium-dependent vasorelaxation of the aortic rings, and heart function were studied. We demonstrate that our combination increased H2S syntheses by 13 times and cNOS activity by 5 times in the heart tissue of diabetic rats. Increasing NO and H2S production caused improving and restoration of endothelium-dependent relaxation of aorta, effective arterial elastance, and diastolic heart function in diabetic rats. The endothelium-dependent relaxation increased by 2.4 times; effective arterial elastance decreased by 47%. The end-diastolic myocardial stiffness decreased by 2.2 times. Thus, modulation of hydrogen sulfide synthesis leads to increased activity cNOS by 5 times in the cardiovascular system. Increasing NO and H2S production restored endothelium-dependent relaxation of aorta and improved heart function in diabetes.


2019 ◽  
Vol 106 (1) ◽  
pp. 48-58 ◽  
Author(s):  
L Chodari ◽  
H Dariushnejad ◽  
V Ghorbanzadeh

Objective Low levels of testosterone in men with diabetes are associated with cardiovascular complications. We investigated the effect of testosterone and voluntary exercise on heart angiogenesis in castrated diabetic rats. Methods Sixty-three diabetic rats were treated with testosterone 2 mg/kg/day or voluntary exercise alone or combination of these two for 6 weeks. At the end of the study, heart tissue samples were collected and used for CD31 detection by immunohistochemical method and determination of miR-132 levels. Results miR-132 levels and CD31 of heart tissue were higher after testosterone administration and in the voluntary exercise group in diabetic rats after 6 weeks. Combination of testosterone and voluntary exercise had synergistic effect on angiogenesis and miR-132 level. In castrated diabetic rats, there were significantly lower levels of miR-132 and CD31 in heart tissue compared to the diabetic group, whereas testosterone and exercise reversed these effects. In addition, testosterone supplementation plus exercise had an additive effect on miR-132 levels and CD31 in castrated diabetic rats. Conclusions It was concluded that castration in rats leads to reduced miR-132 levels and subsequently decreased angiogenesis in diabetes. Testosterone plus voluntary exercise improved angiogenesis possibly through enhancement of miR-132 levels in heart of castrated diabetic rats.



2000 ◽  
Vol 78 (5) ◽  
pp. 415-422 ◽  
Author(s):  
Ying-I Peng ◽  
Kuo-Chu Chang

We determined the acute effects of methoxamine, a specific alpha1-selective adrenoceptor agonist, on the left ventricular-arterial coupling in streptozotocin (STZ)-diabetic rats, using the end-systolic pressure-stroke volume relationships. Rats given STZ 65 mg·kg-1 iv (n = 8) were compared with untreated age-matched controls (n = 8). A high-fidelity pressure sensor and an electromagnetic flow probe measured left ventricular (LV) pressure and ascending aortic flow, respectively. Both LV end-systolic elastance ELV,ES and effective arterial elastance Ea were estimated from the pressure-ejected volume loop. The optimal afterload Qload determined by the ratio of Ea to ELV,ES was used to measure the optimality of energy transmission from the left ventricle to the arterial system. In comparison with controls, diabetic rats had decreased LV end-systolic elastance ELV,ES, at 513 ± 30 vs. 613 ± 29 mmHg·mL-1, decreased effective arterial elastance Ea, at 296 ± 20 vs. 572 ± 48 mmHg·mL-1, and decreased optimal afterload Qload, at 0.938 ± 0.007 vs. 0.985 ± 0.009. Methoxamine administration to STZ-diabetic rats significantly increased LV end-systolic elastance ELV,ES, from 513 ± 30 to 602 ± 38 mmHg·mL-1, and effective arterial elastance Ea, from 296 ± 20 to 371 ± 28 mmHg·mL-1, but did not change optimal afterload Qload. We conclude that diabetes worsens not only the contractile function of the left ventricle, but also the matching condition for the left ventricular-arterial coupling. In STZ-diabetic rats, administration of methoxamine improves the contractile status of the ventricle and arteries, but not the optimality of energy transmission from the left ventricle to the arterial system. Key words: streptozotocin-diabetic rats, left ventricular-arterial coupling, left ventricular end-systolic elastance, effective arterial elastance, optimal afterload.





1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill

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.



2017 ◽  
Vol 2 (4) ◽  
pp. 172-177
Author(s):  
Saeid Tanoorsaz ◽  
Naser Behpoor ◽  
Vahid Tadibi

Introduction: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of caspase-8, Bcl-2, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cardiac tissue after 4 weeks of aerobic exercise in male rats with diabetes. Methods: Forty adult male rats were randomly allocated to healthy control, diabetes, control + exercise and exercise + diabetes groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg). Two weeks after injection, fasting blood glucose levels were measured. After the induction of diabetes, the exercise program was performed for 4 weeks (5 sessions per week) at a speed of 15 to 18 m/min for 25 to 44 minutes. Forty-eight hours after the last training session, the subjects were anesthetized and the heart muscle was removed. Caspase-8, Bcl-2 and NT-proBNP levels were measured by ELISA method. Results: The induction of diabetes in the control group resulted in a significant increase in caspase-8, and NT-proBNP levels while an insignificant increase was observed for Bcl-2 levels (P<0.05). In non-diabetic groups, exercise caused no changes in caspase-8, NT-proBNP and Bcl-2 (P<0.05). Exercise in diabetic groups significantly decreased NT-proBNP while no changes were observed in caspase-8 and Bcl-2 (P<0.05). Conclusion: Our findings showed that diabetes increases the pro-apoptotic and anti-apoptotic agent. In addition, 4 weeks of regular aerobic exercises can be used as a non-pharmacological strategy to reduce the complications of apoptosis in diabetic cardiomyocytes.



2020 ◽  
Author(s):  
Angelo Gaitas ◽  
Francesca Stillitano ◽  
Irene Turnbull

AbstractCardiomyocytes iPSC (iPSC-CMs) have great potential for cell therapy, drug assessment, and for understanding the pathophysiology and genetic underpinnings of cardiac diseases. Contraction forces are one of the most important characteristics of cardiac function and are predictors of healthy and diseased states. Cantilever techniques, such as atomic force microscopy, measure the vertical force of a single cell, while systems designed to more closely resemble the physical heart function, such as cardiac tissue on posts, measure the axial force. One important question is how do these two force measurements correlate? By establishing a correlation of the axial and vertical force we will be one step closer in being able to use single cell iPSC instead of more elaborate human engineered tissue or animal heart tissue as models. A novel micromachined sensor for measuring force contractions of artificial tissue has been developed. Using this novel sensor a correlation between axial force and vertical force is experimentally established. This finding supports the use of vertical measurements as an alternative to tissue measurements.



2010 ◽  
Vol 42 ◽  
pp. 541
Author(s):  
Christopher Fahs ◽  
Lindy Rossow ◽  
Huimin Yan ◽  
Sushant M. Ranadive ◽  
Stamatis Agiovlasitis ◽  
...  


2014 ◽  
Vol 33 (4) ◽  
pp. S143
Author(s):  
Z. Daniels ◽  
C. Del Rio ◽  
B. Youngblood ◽  
R.S. George ◽  
Y. Ueyama ◽  
...  


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