Effects of omeprazole on the production of nitric oxide metabolites and nitrite-induced cardiac protection

• Grant number: 19/22162-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Daniele Gonçalves Grieco
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Treatment with oral nitrite, by supplementing the alternative nitric oxide (NO) formation pathway called nitrate-nitrite-NO, has beneficial effects for cardiovascular homeostasis in various disorders. Sodium nitrite establishes a city and cardioprotective effect against myocardial ischemia and reperfusion injury, together with an increase in nitrosothiols, nitrosylated proteins and the conversion of nitrite to NO with the participation of the nitrate-nitrite-NO pathway. Gastric pH is a determining factor in this pathway, so treatment with omeprazole attenuates the formation of NO-related species that contribute to the effect of oral nitrite. We then aimed to determine whether treatment with omeprazole inhibits sodium nitrite-induced cardiac protection in the ischemia/reperfusion model. For this, we will use C57BL/6J mice (10-12 weeks), divided into 6 groups of different treatments (Vehicle tween 2% orally; Sodium nitrite 1 mg/kg orally; Omeprazole 20mg / kg intraperitoneal), which in turn are subdivided into two groups: Sham groups (without I / R induction): Sham + Vehicle, Sham + Nitrite, Sham + Nitrite + Omeprazole; and I/R groups (under I / R action*): I / R + Vehicle, I / R + Nitrite, I / R + Nitrite + Omeprazole. Following I/R induction and treatment, the animals will be anesthetized with intraperitoneal ketamine and xylazine (120 mg/kg and 5 mg/kg respectively), the heart will be collected for histological and biochemical assays to determine tissue nitrite concentrations and nitrosylated species, as well as evaluation of nitrosylated proteins. Results will be analyzed by two-way analysis of variance (two way ANOVA) followed by Newman-Keuls post-test.