Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. Free Radic Biol Med 2012 Jan 15;52(2):427-35
Date
11/01/2011Pubmed ID
22037515Pubmed Central ID
PMC3432314DOI
10.1016/j.freeradbiomed.2011.09.020Scopus ID
2-s2.0-84855460214 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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 (1-50nM). 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.
Author List
Mao M, Sudhahar V, Ansenberger-Fricano K, Fernandes DC, Tanaka LY, Fukai T, Laurindo FR, Mason RP, Vasquez-Vivar J, Minshall RD, Stadler K, Bonini MGAuthor
Jeannette M. Vasquez-Vivar PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AndrostadienesAnimals
Aorta
Blood Pressure
Cattle
Cells, Cultured
Endothelial Cells
Enzyme Activation
Humans
In Vitro Techniques
Male
Mice
Microvessels
Nitric Oxide
Nitric Oxide Synthase Type III
Nitroglycerin
PTEN Phosphohydrolase
Phosphatidylinositol 3-Kinase
Phosphatidylinositol Phosphates
Phosphorylation
Proto-Oncogene Proteins c-akt
Rats
Rats, Sprague-Dawley
Signal Transduction
Vasodilation
Vasodilator Agents
