Acute inhibition of superoxide formation and Rac1 activation by nitric oxide and iloprost in human vascular smooth muscle cells in response to the thromboxane A2 analogue, U46619.

Prostaglandins, Leukotrienes, and Essential Fatty Acids
S MuzaffarJ Y Jeremy

Abstract

The over-production of superoxide (O(2)(-)) derived from NADPH oxidase (NOX) plays a central role in cardiovascular diseases. By contrast, nitric oxide (NO) and prostacyclin (PGI(2)) are vasculoprotective. The effect of the NO donor, NONOate and iloprost on O(2)(-) formation, p47(phox) and Rac(1) activation in human vascular smooth muscle cells (hVSMCs) was investigated. hVSMCs were incubated with 10nM thromboxane A(2) analogue, U46619 for 16h, and then with apocynin (a NOX inhibitor), NONOate or iloprost for 1h and O(2)(-) measured spectrophometrically. The role of cyclic AMP and cyclic GMP was examined by co-incubation of drugs with protein kinase (PK) A and G inhibitors listed above. Rac(1) was studied using pull-down assays. NONOate and iloprost inhibited O(2)(-) formation, acutely, effects blocked by inhibition of PKG and PKA, respectively. Rac(1) and p47(phox) activation and translocation to the plasma membrane was completely inhibited by NONOate and iloprost, effects again reversed by co-incubation with PKG or PKA inhibitors. NO and PGI(2) block the acute activity of NOX in hVSMCs via the cGMP-PKG axis (for NO) and by the cAMP-PKA axis (for iloprost) through inhibition of Rac(1) and p47(phox) translocation. These finding...Continue Reading

References

Mar 1, 1988·Prostaglandins, Leukotrienes, and Essential Fatty Acids·D P MikhailidisP Dandona
Mar 23, 2000·Cardiovascular Research·J Y JeremyK M Naseem
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·W R DostmannW J Tegge
Aug 15, 2002·American Journal of Physiology. Cell Physiology·Asha JacobNajma Begum
Sep 12, 2003·Trends in Pharmacological Sciences·Hua CaiDavid G Harrison
Apr 16, 2004·Heart·A M Shah, K M Channon
Aug 24, 2004·Current Vascular Pharmacology·Jamie Y JeremyGianni D Angelini
Oct 12, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jian-Mei Li, Ajay M Shah
Oct 30, 2004·The Journal of Biological Chemistry·Ahmed ChahdiAndrey Sorokin
Feb 12, 2005·Journal of Cellular Physiology·Stéphane PelletierSylvain Meloche
Nov 22, 2005·Trends in Cardiovascular Medicine·Saima MuzaffarJamie Y Jeremy
Feb 1, 2006·The Journal of Biological Chemistry·Eva N Christensen, Michael E Mendelsohn
Mar 4, 2006·Circulation Research·Peter L Hordijk
Apr 1, 2006·Circulation Research·Joan Heller BrownMark A Sussman
Jun 20, 2006·Cardiovascular Research·Leni MoldovanLisa L Satterwhite
Oct 21, 2006·International Journal of Impotence Research·J Y JeremyN Shukla
Apr 3, 2007·British Journal of Pharmacology·M R Miller, I L Megson
Jan 25, 2008·American Journal of Physiology. Renal Physiology·Lorena BlancoAdolfo Varona
Feb 10, 2010·Thrombosis and Haemostasis·Karsten SchrörArtur-Aron Weber

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Citations

Apr 29, 2010·Current Hypertension Reports·Paul M O'Connor, Allen W Cowley
Sep 18, 2010·Journal of Hypertension·Olga Pechanova, Fedor Simko
Apr 1, 2011·American Journal of Physiology. Cell Physiology·Chittaranjan RoutrayNingling Kang
Nov 20, 2012·American Journal of Physiology. Heart and Circulatory Physiology·M A Hassan TalukderJay L Zweier
Feb 27, 2009·American Journal of Physiology. Renal Physiology·Nancy J Hong, Jeffrey L Garvin
Nov 9, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jamie Y JeremySong Wan
Apr 17, 2012·Current Opinion in Pharmacology·Helen WeaverJamie Y Jeremy
Jun 13, 2012·Hypertension·Renate B SchnabelUNKNOWN Gutenberg Health Study Investigators
Jul 7, 2011·Journal of Cellular Physiology·Saima MuzaffarNilima Shukla
Jul 26, 2013·American Journal of Physiology. Renal Physiology·Nicholas G MossWilliam J Arendshorst
Dec 17, 2014·American Journal of Physiology. Renal Physiology·Nancy J Hong, Jeffrey L Garvin
May 1, 2021·Frontiers in Cardiovascular Medicine·Mario Álvarez-MaestroMercedes Ferrer
Jul 31, 2021·Clinical and Experimental Pharmacology & Physiology·Jeimison D SantosLusiane M Bendhack

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