Antagonism of LPS and IFN-gamma induction of iNOS in human saphenous vein endothelium by morphine and anandamide by nitric oxide inhibition of adenylate cyclase

Journal of Cardiovascular Pharmacology
G B StefanoT V Bilfinger

Abstract

Nitric oxide (NO) production regulates vasodilation in many blood vessels. Additionally, constitutive NO release is being associated with positive biomedical phenomena, whereas inducible NO synthase (iNOS)-associated NO release with detrimental consequences in regard to endothelial inflammatory activities. As yet, an important link demonstrating why one is activated over the other is not available. Previous studies have demonstrated that morphine and anandamide effector processes are coupled to NO release in human endothelial cells (ECs). This study now extends this observation in that these endogenous signaling molecules may use NO directly to inhibit adenylate cyclase activity. Activation of human ECs, obtained from the saphenous vein, with morphine- or anandamide-stimulated NO release (35 nM and 28 nM, respectively) that peaked within 5 min and returned to basal levels within 10 min of agonist stimulation, consistent with constitutive NO synthase (cNOS) activation. Significant release of NO from ECs stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) occurred after 2 h after exposure and remained significantly increased over basal levels for 24-48 h (28 nM), consistent with iNOS activation. Preincubatio...Continue Reading

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Citations

Nov 19, 2009·Journal of Anesthesia·Noboru TodaHiroshi Toda
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Allyn C HowlettDerek C Norford
Dec 7, 2000·Chemistry and Physics of Lipids·A C Howlett, S Mukhopadhyay
Nov 16, 2002·Prostaglandins & Other Lipid Mediators·Allyn C Howlett
Jun 15, 1999·Prostaglandins & Other Lipid Mediators·C FimianiG B Stefano
Dec 13, 2000·Brain Research. Brain Research Reviews·J C de la Torre, G B Stefano
Mar 14, 2001·Brain Research. Brain Research Reviews·G B StefanoH Benson
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Aug 1, 1998·International Journal of Cardiology·T V BilfingerG B Stefano
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Mar 23, 2005·Acta Pharmacologica Sinica·Elliott SalamonGeorge B Stefano
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Sep 9, 2008·Neurochemical Research·George B StefanoWei Zhu

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