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Study of the post-translational mechanisms involved on increased nitric oxide bioavailability in spotaneoulsy hypertensive rats treated with apocynin

Grant number: 17/18436-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristina Antoniali Silva
Grantee:Murilo Eduardo Graton
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated scholarship(s):19/13751-0 - Role of histones on cardiac dysfunction in sepsis-induced cardiomyopathy, BE.EP.DR


Nitric Oxide (NO) is the major vasodilator molecule in the body and it is synthesized by the NO synthase enzymes, and the isoform III or endothelial (eNOS) is the main responsible for the production of NO in the blood vessels. Increased production of Reactive Oxygen Species (ROS) by oxidative enzymes such as NOX enzymes can lead to oxidative stress and reduce NO bioavailability. We have recently shown that apocynin, a NOX inhibitor, is able to increase eNOS expression and activity and NO bioavailability in spontaneously hypertensive rats (SHR). The objective of this work will be to evaluate the possible changes in post-translational modification mechanisms that control eNOS and the bioavailability of NO in SHR treated with apocynin (30 mg / kg, p.o.). Western Blotting assays will be performed for the evaluation of the protein expression of eNOS, calmodulin, caveolin-1, Hsp-90, Nrf-2, catalase, superoxide dismutase and glutathione peroxidase, as well as their interactions through co-immunoprecipitation. Functional studies of vascular reactivity in mesenteric artery rings to evaluate the participation of Hsp-90 and eNOS in vasoconstriction induced by phenylephrine. The intracellular concentrations of hydrogen peroxide will be quantified by flow cytometry. The results obtained will be expressed as mean ± SEM and statistically analyzed by statistical analysis of one-way ANOVA or Student's T Test and a significance level of 5% (p <0.05) will be adopted. (AU)