Study of antihypertensive mechanisms of sodium nitrite in experimental renovascular hypertension

Author(s)

Lucas Cézar Pinheiro

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2014-12-18

Examining board members

Jose Eduardo Tanus dos Santos; Julio Sérgio Marchini; José Carlos Toledo Junior

• Advisor: Jose Eduardo Tanus dos Santos

Abstract

Nitric Oxide plays many functional roles in physiological systems. In the cardiovascular system it participates in a unique way in the regulation of vascular tone among other functions. Dysfunctions in the production or availability of NO may compromise their physiological activity and participate in hypertension. Besides the production of NO by the nitric oxide synthase, other physiological pathways of NO production from nitrite have been described. The nitrite and nitrate are oxidation products of NO. Further nitrite is oxidized to nitrate. These three molecules are known to forma cycle in the body. Nitrate is excreted in saliva and reduced to nitrite by oral bacteria. Nitrite then is swallowed with the saliva and exerts its effects through conversion to NO. The conversion of nitrite to NO may occur by enzymatic or non-enzymatic manner. As a non-enzymatic way nitrite is reduced to NO by reaction with H+.This reaction occurs mainly in the stomach. This thesis aims to elucidate possible mechanisms responsible for the antihypertensive effects of sodium nitrite. We studied 2K1C rats treated with nitrite and nitrate and checked anti-hypertensive effects of these molecules. The increased gastric pH by omeprazole prevented the anti-hypertensive effect of nitrite and nitrate. Omeprazole did not cause any differences in plasma nitrite and nitrate. It was found that treatment with nitrite and nitrate resulted inincreased nitrosylated species in the plasma, and this increase was blocked by omeprazole. We also tested the influence of the entero-salivarycycle effect of nitrite and nitrate. We found that treatment with mouthwash blunted the antihypertensive effect of nitrate but this effect did not change in animals treated with nitrite. Interestingly in all experimental approaches the anti-hypertensive effect of nitrite only occurred when there was an increase in the plasma concentration of nitrosylated species (AU)

• FAPESP's process: 11/10921-0 - Study of antihypertensive mechanism of sodium nitrite in experimental renovascular hypertension
• Grantee: Lucas Cezar Pinheiro
• Support Opportunities: Scholarships in Brazil - Doctorate