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Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy.

Authors
  • Oliveira-Paula, Gustavo H1
  • Tanus-Santos, Jose E1
  • 1 Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. , (Brazil)
Type
Published Article
Journal
Current drug targets
Publication Date
Jan 01, 2019
Volume
20
Issue
4
Pages
431–443
Identifiers
DOI: 10.2174/1389450119666180816120816
PMID: 30112990
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. While enzymes with nitrite-reductase activity capable of generating NO from nitrite may contribute to antihypertensive effects of nitrite, another mechanism involving the generation of NO-related species in the stomach from nitrite has been validated. Under the acidic conditions of the stomach, nitrite generates NO-related species that form S-nitrosothiols. Conversely, drugs that increase gastric pH may impair the gastric formation of S-nitrosothiols, which may mediate antihypertensive effects of oral nitrite or nitrate. Therefore, it is now becoming clear that promoting gastric formation of S-nitrosothiols may result in effective antihypertensive responses, and this mechanism opens a window of opportunity in the therapy of hypertension. In this review, we discuss the recent studies supporting the gastric generation of S-nitrosothiols as a potential antihypertensive mechanism of oral nitrite. We also highlight some drugs that increase S-nitrosothiols bioavailability, which may also improve the responses to nitrite/nitrate therapy. This new approach may result in increased nitrosation of critical pharmacological receptors and enzymes involved in the pathogenesis of hypertension, which tend to respond less to their activators resulting in lower blood pressure. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]

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