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

Mao Mao, Varadarajan Sudhahar, 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

20 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Mao, M., Sudhahar, V., Ansenberger-Fricano, K., Fernandes, D. C., Tanaka, L. Y., Fukai, T., Laurindo, F. R. M., Mason, R. P., Vasquez-Vivar, J., Minshall, R. D., Stadler, K., & Bonini, M. G. (2012). Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. Free Radical Biology and Medicine, 52(2), 427-435. https://doi.org/10.1016/j.freeradbiomed.2011.09.020