Antioxidants but not Doxycycline Treatments Restore Depressed Beta-Adrenergic Responses of the Heart in Diabetic Rats

Abstract

Reactive oxygen species (ROS) play important roles in the development of diabetic cardiomyopathy. Matrix metalloproteinases (MMPs) can get activated by ROS and contribute to loss of myocardial contractile function in oxidative stress injury. Previously we have shown that either a MMP-2 inhibitor doxycycline or an antioxidant selenium treatment in vivo prevented diabetes-induced cardiac dysfunction significantly. In addition, there is an evidence for impaired cardiac responsiveness to beta-adrenoceptor (beta AR) stimulation in experimental animals with diabetes. The exact nature of linkage between the functional depression in cardiac responses to catecholamines and the variations in uncoupling of beta AR in diabetes has not been clearly defined. Therefore, we aimed to evaluate the effect of in vivo administration of doxycycline on beta AR responses of isolated hearts from diabetic rats and compare these data with two well-known antioxidants; sodium selenate and (n-3) fatty acid-treated diabetic rats. We examined the changes in the basal cardiac function in response to the beta AR stimulation, adenylate cyclase activity, and beta AR affinity to its agonist, isoproterenol. These results showed that antioxidant treatment of diabetic rats could protect the hearts against diabetes-induced depression in beta AR responses, significantly while doxycycline did not have any significant beneficial action on these parameters. As a summary, present data, in part, demonstrate that antioxidants and MMP inhibitors could both regulate MMP function but may also utilize different mechanisms of action in cardiomyocytes, particularly related with beta AR signaling pathway.

Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2, FKBP12.6, and SERCA2a in rats

“…Increased oxidative stress in vivo has been shown to contribute to the pathogenesis of diabetic cardiomyopathy [24,25] . MDA, a lipid oxidation end product, affects the mitochondrial respiratory chain complex and the activities of key enzymes in the mitochondria.…”

Attenuation of beta2-adrenergic receptors and homocysteine metabolic enzymes cause diabetic cardiomyopathy

“…The pharmacological beta-AR agonist and blockers are in clinical practice for maintaining the sympathetic drive in cardiovascular diseases [4;29]. The empirical evidences suggest their role in diabetic cardiomyopathy [3].…”

Glycolaldehyde Induces Oxidative Stress in the Heart: A Clue to Diabetic Cardiomyopathy?

“…Increased carbonyl content of the heart has been observed in diabetic animals [15,17,42]. Furthermore, antioxidant treatments restore cardiac function after diabetes induction [43,44]. We also assessed the plasma activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase (data not shown), which are common markers of hepatic and heart dysfunction.…”