Acute activation of eNOS by statins involves scavenger receptor-B1, G protein subunit Gi, phospholipase C and calcium influx.

British Journal of Pharmacology
R DatarR W Caldwell

Abstract

Statins (HMG CoA reductase inhibitors) have beneficial effects independent of reducing cholesterol synthesis and this includes their ability to acutely activate endothelial nitric oxide synthase (eNOS). The mechanism by which this occurs is largely unknown and thus we characterized the pathways by which statins activate NOS, including involvement of scavenger receptor-B1 (SR-B1), which is expressed in endothelial cells and maintains cholesterol concentrations. Nitric oxide production was monitored in bovine aortic endothelial cells (BAECs) exposed to lovastatin (LOV) or pravastatin (PRA) for 10-20 min, alone or following pre-exposure to the end product of HMG-CoA reductase (mevalonate), G protein inhibitors (pertussis/cholera toxins), phospholipase C (PLC) inhibitor (U-73122), or intracellular and extracellular calcium chelators - BAPTA-AM and EGTA (respectively), or a function blocking antibody to SR-B1. Both statins increased NO production in a rapid, dose-dependent and HMG-CoA reductase-independent manner. Inhibiting Gi protein or PLC almost completely blocked statin-induced NO generation. Additionally, removing extracellular calcium inhibited statin-induced NO production. COS-7 cells co-transfected with eNOS and SR-B1 incre...Continue Reading

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Citations

Dec 27, 2011·Cellular and Molecular Neurobiology·Kirtiman SrivastavaUlvi Bayraktutan
Dec 18, 2013·European Journal of Pharmacology·Yonghong LiShanglang Cai
Dec 10, 2013·The Journal of Veterinary Medical Science·Shinji AritaYoshiaki Hikasa
Jul 13, 2012·Clinical and Experimental Hypertension : CHE·Frank Holden MoseErling Bjerregaard Pedersen
Aug 6, 2013·Scandinavian Cardiovascular Journal : SCJ·Ott SaluveerBengt R Widgren
Mar 20, 2016·Atherosclerosis·Paul A Cahill, Eileen M Redmond
Mar 16, 2013·British Journal of Pharmacology·A Tran-DinhO Meilhac
Jul 17, 2012·European Journal of Pharmacology·Chukwuemeka O UhiaraRichard E Roberts
May 21, 2013·Journal of Molecular and Cellular Cardiology·George VaniotisBruce G Allen
Oct 5, 2011·Journal of Molecular and Cellular Cardiology·Pitchai BalakumarNanjaian Mahadevan
Dec 27, 2015·Acta Physiologica·P M VanhoutteE H C Tang
Nov 6, 2014·Experimental and Therapeutic Medicine·Dilidaer XilifuXiangyang Zhang
Feb 22, 2012·Nature Reviews. Endocrinology·Julia C CreiderTisha R Joy

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