Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation

Marcelo G. Bonini, Krisztian Stadler, Sueli De Oliveira Silva, Jean Corbett, Michael Dore, John Petranka, Denise C. Fernandes, Leonardo Y. Tanaka, Danielle Duma, Francisco R.M. Laurindo, Ronald P. Mason

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major source of NO responsible for low-dose (1-10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals.

Original languageEnglish (US)
Pages (from-to)8569-8574
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number25
DOIs
StatePublished - Jun 24 2008
Externally publishedYes

Keywords

  • Blood pressure
  • Endothelial NOS
  • Neuronal NOS

ASJC Scopus subject areas

  • General

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