Disrupting role of lead toxicity in heart functions and prognosis of cardiovascular diseases is not well known. This study investigated the interference of lead in heart functions and pacing postconditioning-mediated protection to the heart from ischemia-reperfusion injury. Lead exposure decreased the body weight and increased the heart weight in male rats (p < 0.001). Long-term lead exposure (45 days exposure to lead) increased total oxidant levels (p < 0.001) in the heart. Furthermore, lead exposure abrogated the pacing postconditioning-mediated protection from ischemia-reperfusion injury. The latter effect showed an association with reduced total antioxidants levels (p < 0.001). In the short-term study (5 days exposure to lead), pacing postconditioning protected the heart from ischemia-reperfusion injury despite the reduced total antioxidant levels (p < 0.001). Lead toxicity caused a drastic increase in the heart weight in male rats and apoptosis. The induced oxidative stress showed association with the lack of pacing postconditioning-mediated protection of the heart. However, long-term lead exposure eliminated pacing postconditioning-mediated protection of the heart from ischemia-reperfusion injury.

Background: Diabetes mellitus (DM) is a risk factor for cardiovascular diseases, specifically, the ischemic heart diseases (IHD). The renin–angiotensin system (RAS) affects the heart directly and indirectly. However, its role in the protection of the heart against I/R injury is not completely understood. The aim of the current study was to evaluate the efficacy of the angiotensin-converting enzyme (ACE) inhibitor and Angiotensin II receptor (AT1R) blocker or a combination thereof in protection of the heart from I/R injury. Methods: Hearts isolated from adult male Wistar rats (n = 8) were subjected to high glucose levels; acute hyperglycemia or streptozotocin (STZ)-induced diabetes were used in this study. Hearts were subjected to I/R injury, treated with Captopril, an ACE inhibitor; Losartan, an AT1R antagonist; or a combination thereof. Hemodynamics data were measured using a suitable software for that purpose. Additionally, infarct size was evaluated using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. The levels of apoptosis markers (caspase-3 and -8), antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), nitric oxide synthase (eNOS), and glucose transporter type 4 (GLUT-4) protein levels were evaluated by Western blotting. Pro-inflammatory and anti-inflammatory cytokines levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results: Captopril and Losartan alone or in combination abolished the effect of I/R injury in hearts subjected to acute hyperglycemia or STZ-induced diabetes. There was a significant (p < 0.05) recovery in hemodynamics, infarct size, and apoptosis markers following the treatment with Captopril, Losartan, or their combination. Treatment with Captopril, Losartan, or their combination significantly (p < 0.05) reduced pro-inflammatory cytokines and increased GLUT-4 protein levels. Conclusions: The blockade of the RAS system protected the diabetic heart from I/R injury. This protection followed a pathway that utilizes GLUT-4 to decrease the apoptosis markers, pro-inflammatory cytokines, and to increase the anti-inflammatory cytokines. This protection seems to employ a pathway which is not involving ERK1/2 and eNOS.

No abstract