Effects of Nitrate Intake on Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

Abstract

BackgroundCoronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated.ObjectiveWe examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats.MethodRats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx).ResultsRecovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake.ConclusionDietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.

Evaluation of ameliorative effect of sodium nitrate in experimental model of streptozotocin-induced diabetic neuropathy in male rats

“…Alteration of serum NO concentrations in diabetic conditions are controversial. Some studies have demonstrated that serum NO levels decreased in diabetic rats (Meininger et al 2000;Jeddi et al 2016). On the other hand, other studies have shown increased or unchanged NO levels in diabetes (Mancusi et al 1996;Milsom et al 2002;Adela et al 2015).…”

“…A recent study stated that an increased incidence of diabetes among children may be related to high nitrate concentrations in drinking water, however, other studies have shown beneficial effects of nitrate (Benson et al 2010). In addition, chronic intake of a low dose of nitrate (100 mg/l/day) for 2 months protected the diabetic rat heart from ischemia-reperfusion injury by attenuating oxidative stress (Jeddi et al 2016). Cardiac and renal protective effects of vegetables may relate to their high nitrate contents (Lundberg et al 2006;Ohtake et al 2007).…”

Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin‐induced diabetic male rats

“…The insulin dose was adjusted in accordance with the blood glucose level. Animals in the nitrate groups received sodium nitrate (Merck KGaA, Darmstadt, Germany) added to their drinking water supplemented with 100 mg l −1 sodium nitrate for 2 months (Jeddi, Khalifi, Ghanbari, Bageripour, & Ghasemi, ). The water intake was measured every day.…”

“…Germany) added to their drinking water supplemented with 100 mg l −1 sodium nitrate for 2 months (Jeddi, Khalifi, Ghanbari, Bageripour, & Ghasemi, 2016). The water intake was measured every day.…”

Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities

“…Despite the fact that NaNO 2 has not been reliable in the past and has the potential to cause many cancers, it has recently been reported that it can prevent myocardial ischemia-reperfusion injury in diabetic rats by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart [50]. It also prevents hypertension and increases endotheliumdependent relaxation and total NO by regulating eNOS activity [51].…”