Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

Mao Mao, Sudhahar Varadarajan, Kristine Ansenberger-Fricano, Denise C. Fernandes, Leonardo Y. Tanaka, Tohru Fukai, Francisco R.M. Laurindo, Ronald P. Mason, Jeannette Vasquez-Vivar, Richard D. Minshall, Krisztian Stadler, Marcelo G. Bonini

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1-50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin- dependent accumulation of 3,4,5-InsP 3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses.

Original languageEnglish (US)
Pages (from-to)427-435
Number of pages9
JournalFree Radical Biology and Medicine
Volume52
Issue number2
DOIs
StatePublished - Jan 15 2012
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Nitric Oxide Synthase Type III
Nitroglycerin
Chemical activation
Pharmacology
Chromosomes, Human, Pair 10
Signal transduction
Angina Pectoris
Chromosomes
Phosphoric Monoester Hydrolases
Vasodilation
Signal Transduction
Nitric Oxide
Research

Keywords

  • Akt
  • Free radicals
  • Glyceryl trinitrate
  • Nitric oxide
  • Nitroglycerin
  • PI3K
  • eNOS

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. / Mao, Mao; Varadarajan, Sudhahar; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R.M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.

In: Free Radical Biology and Medicine, Vol. 52, No. 2, 15.01.2012, p. 427-435.

Research output: Contribution to journalArticle

Mao, M, Varadarajan, S, Ansenberger-Fricano, K, Fernandes, DC, Tanaka, LY, Fukai, T, Laurindo, FRM, Mason, RP, Vasquez-Vivar, J, Minshall, RD, Stadler, K & Bonini, MG 2012, 'Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway', Free Radical Biology and Medicine, vol. 52, no. 2, pp. 427-435. https://doi.org/10.1016/j.freeradbiomed.2011.09.020
Mao, Mao ; Varadarajan, Sudhahar ; Ansenberger-Fricano, Kristine ; Fernandes, Denise C. ; Tanaka, Leonardo Y. ; Fukai, Tohru ; Laurindo, Francisco R.M. ; Mason, Ronald P. ; Vasquez-Vivar, Jeannette ; Minshall, Richard D. ; Stadler, Krisztian ; Bonini, Marcelo G. / Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. In: Free Radical Biology and Medicine. 2012 ; Vol. 52, No. 2. pp. 427-435.
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