Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation. Proc Natl Acad Sci U S A 2008 Jun 24;105(25):8569-74
Date
06/20/2008Pubmed ID
18562300Pubmed Central ID
PMC2438390DOI
10.1073/pnas.0708615105Scopus ID
2-s2.0-47249141931 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Bonini MG, Stadler K, Silva SO, Corbett J, Dore M, Petranka J, Fernandes DC, Tanaka LY, Duma D, Laurindo FR, Mason RPMESH terms used to index this publication - Major topics in bold
AnimalsCells, Cultured
Endothelium, Vascular
Enzyme Inhibitors
Humans
Male
Mice
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Nitroglycerin
Phosphorylation
Rats
Rats, Sprague-Dawley
Time Factors
Vasodilation
Vasodilator Agents
