Anadolu Kardiyoloji Dergisi, Anadolu Kardiyol Derg, The Anatolian Journal of Cardiology, Anatol J Cardiol, Cardiology, Cardiovascular Medicine, Surgery, Pediatric Cardiology, Angiology

Epoxyeicosatrienoic acids (EETs) and their analogs have been identified as potent antihypertensive compounds with cardio- and renoprotective actions. Here, we examined the effect of EET-A, an orally active EET analog, and c-AUCB, an inhibitor of the EETs degrading enzyme soluble epoxide hydrolase, on the progression of post-myocardial infarction (MI) heart failure (HF) in normotensive Hannover Sprague-Dawley (HanSD) and in heterozygous Ren-2 transgenic rats (TGR) with angiotensin II-dependent hypertension. Adult male rats (12 weeks old) were subjected to 60-min left anterior descending (LAD) coronary artery occlusion or sham (non-MI) operation. Animals were treated with EET-A and c-AUCB (10 and 1 mg/kg/day, respectively) in drinking water, given alone or combined for 5 weeks starting 24 h after MI induction. Left ventricle (LV) function and geometry were assessed by echocardiography before MI and during the progression of HF. At the end of the study, LV function was determined by catheterization and tissue samples were collected. Ischemic mortality due to the incidence of sustained ventricular fibrillation was significantly higher in TGR than in HanSD rats (35.4 and 17.7%, respectively). MI-induced HF markedly increased LV end-diastolic pressure (P_ed) and reduced fractional shortening (FS) and the peak rate of pressure development [+(dP/dt)_max] in untreated HanSD compared to sham (non-MI) group [P_ed: 30.5 ± 3.3 vs. 9.7 ± 1.3 mmHg; FS: 11.1 ± 1.0 vs. 40.8 ± 0.5%; +(dP/dt)_max: 3890 ± 291 vs. 5947 ± 309 mmHg/s]. EET-A and c-AUCB, given alone, tended to improve LV function parameters in HanSD rats. Their combination amplified the cardioprotective effect of single therapy and reached significant differences compared to untreated HanSD controls [P_ed: 19.4 ± 2.2 mmHg; FS: 14.9 ± 1.0%; +(dP/dt)_max: 5278 ± 255 mmHg/s]. In TGR, MI resulted in the impairment of LV function like HanSD rats. All treatments reduced the increased level of albuminuria in TGR compared to untreated MI group, but neither single nor combined EET-based therapy improved LV function. Our results indicate that EET-based therapy attenuates the progression of post-MI HF in HanSD, but not in TGR, even though they exhibited renoprotective action in TGR hypertensive rats.

Depressed mechanical activity is a marked complication in diabetics. Hypoxia has properties for novel diagnostic and therapeutic strategies, while intermittent hypoxia (IH) provides early functional and histologic remodeling, including some cardio benefits in early hemodynamic alterations with histologic remodeling and delayed changes in peripheral vasoreactivity. Therefore, we aimed to examine whether IH application presents a cardioprotective effect, via stabilization of hypoxia-inducible factor (HIF) in streptozotocin (STZ)-induced diabetic rat heart. Male 10-week-old Wistar rats were randomly assigned as control group (C), IH group, (STZ)-induced diabetic group (DM) and IH applied DM group (DM+IH). Diabetes duration was kept 6 weeks and IH groups were exposed to hypobaric hypoxia at about 70 kPa (including ~14% PO2; 6 h/day for 6-weeks). Depressed left ventricular developed pressure (LVDP) and prolonged contraction and relaxation of Langendorff-perfused hearts, as well as increased total oxidative status from streptozotocin (STZ)-induced diabetic rats were markedly prevented with IH application. IH application induced significant increase in protein expression levels of both HIF-1α and vascular endothelial growth factor (VEGF), in both control and diabetic rat hearts, whereas there were significant decreases in the protein levels of prolyl-4 hydroxylase domain enzymes, PHD2, and PHD3 in diabetic hearts. Furthermore, IH application induced marked increases in protein levels of matrix metalloproteinases, MMP-2 and MMP-9 and capillary density in left ventricle of diabetic rats. Overall, we presented how IH application has a beneficial cardiovascular remodeling effect in left ventricular function of diabetic rats, at most, via affecting increased oxidative stress and HIF-VEGF related angiogenesis, providing information on hyperglycemia associated new targets and therapeutic strategies.

Diabetes is a metabolic disorder characterized by hyperglycemia and impaired insulin secretion or action. Psychological comorbidities, such as depression and anxiety, are more common in people with diabetes. Exercise results in anxiolytic effects, as demonstrated in numerous studies. This study aims to evaluate potential anxiolytic effects of aerobic exercise in streptozotocin (STZ)-induced diabetes. Male Wistar albino rats (n=40) were randomly divided into four groups of control, exercise, diabetes, and diabetes + exercise. Diabetes was induced with a single i.p. injection of STZ. The incremental load test was applied to exercise groups to determine maximal exercise capacity. Rats exercised on a treadmill at 70% of their maximal capacity for 45 min, five days per week for 12 weeks. On the day after the last exercise session the open field test and elevated plus maze test were carried out. Diabetes caused an increase in anxiety level, reflected in stretch-attend posture, self-grooming behaviors, and freezing time, with no significant changes for other behavioral parameters. Training normalized diabetes-induced deteriorations and also induced a significant anxiolytic effect both on diabetic and non-diabetic rats. This effect was observed for all behavioral parameters. The results of the open field test and elevated plus maze were consistent. The current results demonstrated a slight increase in anxiety with diabetes and a prominent anxiolytic effect of aerobic exercise. Considering the conflicting results in exercise-anxiety studies, this study highlights the importance of individually designed exercise protocols.