Preventive effects of pravastatin on thrombin-triggered vascular responses via Akt/eNOS and RhoA/Rac1 pathways in vivo

Cardiovascular Research
Hiroshi OhkawaraYasuchika Takeishi

Abstract

Small GTPases RhoA and Rac1 play crucial roles in endothelial dysfunction and reactive oxygen species (ROS) generation. We reported evidence that in thrombin-stimulated endothelial cells, rapid geranylgeranylation is an essential process for full activation of unprocessed RhoA, which is blocked by statin. In this study, we examined the effects of intravenous administration of pravastatin on thrombin-triggered vascular responses in vivo, as well as on the lipid modification of unprocessed forms of RhoA and Rac1 and their activation induced by thrombin. Thrombin (50 U/kg) was intravenously injected with or without 0.3 mg/kg pravastatin into Wistar and spontaneously hypertensive rats. Coadministration of pravastatin prevented thrombin-induced impaired endothelium-dependent coronary vasodilation and down-regulated Akt/endothelial nitric oxide synthase (eNOS) phosphorylation within 1 h, as well as the down-regulation of eNOS protein expression within 4 h. In addition, thrombin increased Rac1/p47(phox)-dependent NAD(P)H oxidase activities of rat aortas within 1 h, resulting in ROS generation, which was prevented by the coadministration of pravastatin. Furthermore, the coadministration of pravastatin prevented thrombin-induced convers...Continue Reading

References

Mar 1, 1993·Journal of the American College of Cardiology·R L WilenskyJ A Zeller
Jan 1, 1997·European Journal of Clinical Pharmacology·T W GehrN F Ford
Dec 31, 1997·The Journal of Clinical Investigation·D G Harrison
Sep 3, 1998·The Journal of Biological Chemistry·U Laufs, J K Liao
Jan 14, 1999·The New England Journal of Medicine·R Ross
Feb 9, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Sven WassmannGeorg Nickenig
May 29, 2002·Free Radical Biology & Medicine·Ralf P BrandesRudi Busse
Apr 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Toshiyuki IshibashiYukio Maruyama
Jul 12, 2003·Circulation Research·L VenetucciD A Eisner
Apr 17, 2004·American Journal of Physiology. Heart and Circulatory Physiology·M Brennan HarrisRichard C Venema
Jan 11, 2005·The Journal of Biological Chemistry·Hiroshi OhkawaraYukio Maruyama
Aug 19, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kari T KivistöHeyo K Kroemer
Apr 18, 2006·The American Journal of Cardiology·Tomohiro SakamotoUNKNOWN Multicenter Study for Aggressive Lipid-Lowering Strategy by HMG-CoA Reductase Inhibitors in Patients With Acute Myocardial I
Oct 7, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Shu-ichi SaitohWilliam M Chilian
May 20, 2009·Journal of Cellular Physiology·Nobuo SakamotoYasuchika Takeishi

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Citations

Apr 25, 2014·Journal of Nutritional Science and Vitaminology·Akito MatsushimaMasao Hirayama
Sep 16, 2015·Fukushima Journal of Medical Science·Hiroshi OhkawaraYasuchika Takeishi
Jul 31, 2013·British Journal of Pharmacology·Wen-Han ChengChing-Jiunn Tseng
Apr 14, 2011·British Journal of Pharmacology·G MangialardiP Madeddu
Jan 26, 2011·Journal of Cardiovascular Disease Research·Lin YaoR William Caldwell
Jul 22, 2016·Journal of Cellular Physiology·Chih-Cheng ChangShu-Hui Juan
Sep 5, 2013·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Selvinaz DalakliogluCiler Celik-Ozenci
Nov 24, 2017·Physiological Reviews·Guy EelenPeter Carmeliet
Jul 30, 2019·Oxidative Medicine and Cellular Longevity·Patricia MarchioMaria D Mauricio

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