Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms

European Journal of Pharmacology
Michele M CastroJose E Tanus-Santos

Abstract

Statins have cholesterol-independent effects including an increased vascular nitric oxide (NO) activity and are commonly used by patients with cardiovascular disease. Such patients frequently have erectile dysfunction, which may be treated with sildenafil, a selective inhibitor of phosphodiesterase type 5. Since statins and sildenafil can activate the NO-cGMP pathway, we investigated whether pre-treatment with atorvastatin (0, 5 and 30 mg/kg/day) for 2 weeks affects sildenafil (1 pM-100 mM)-induced relaxation of aortic rings isolated from Wistar rats. We also examined the hemodynamic consequences of this interaction in Wistar rats. Plasma nitrite/nitrate (NOx) concentrations were determined using an ozone-based chemiluminescence assay. While pre-treatment with atorvastatin increased the potency of sildenafil-induced vasorelaxation (P<0.01), no differences were observed in the maximum sildenafil-induced relaxation. Pre-incubation of aortic rings with NG-nitro-L-arginine methyl ester (L-NAME) reversed atorvastatin-induced increase in the potency of sildenafil relaxation. In addition, pre-treatment with atorvastatin enhanced plasma NOx concentrations and sildenafil-induced hypotension and tachycardia (all P<0.05). These results su...Continue Reading

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Citations

Oct 7, 2008·Archives of Toxicology·Elen RizziRaquel F Gerlach
Nov 9, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Diogo M O MarçalJose E Tanus-Santos
Jan 26, 2006·Cardiovascular Drugs and Therapy·Salvatore RosanioYochai Birnbaum
Aug 21, 2009·International Journal of Impotence Research·B G Schwartz, R A Kloner
May 5, 2006·Journal of Human Hypertension·A S Wierzbicki
Aug 3, 2012·American Journal of Physical Medicine & Rehabilitation·Qing Mei WangChristian Waeber
Jun 13, 2014·PloS One·Priscila Portugal Dos SantosSergio Alberto Rupp de Paiva
Jan 23, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Beatrice A Golomb, Marcella A Evans
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Nov 11, 2008·Journal of Endocrinological Investigation·G CoronaM Maggi
Oct 11, 2014·Pharmacogenomics·Riccardo Lacchini, Jose E Tanus-Santos
Jun 2, 2007·Expert Opinion on Drug Metabolism & Toxicology·Antonio AversaGiuseppe M C Rosano
Nov 26, 2014·The Journal of Sexual Medicine·Richard DavisIshak Mansi
Aug 15, 2009·The Journal of Sexual Medicine·Ricardo BorgesFernando Sobral
Aug 29, 2012·The Journal of Sexual Medicine·Lasantha S MalavigeJonathan C Levy
Mar 2, 2010·Pulmonary Pharmacology & Therapeutics·Tuguang KuangChen Wang
Nov 3, 2009·European Journal of Pharmacology·Anna L B Jacob-FerreiraJose E Tanus-Santos
Oct 22, 2008·European Journal of Pharmacology·Marcio L L MartinezJose E Tanus-Santos
Jul 19, 2008·European Journal of Pharmacology·Marcio L L MartinezJose E Tanus-Santos
Oct 16, 2007·The Journal of Urology·Culley C Carson
Aug 21, 2007·European Urology·Charalambos VlachopoulosChristodoulos Stefanadis
May 6, 2009·Basic & Clinical Pharmacology & Toxicology·Marcelo F MontenegroJose E Tanus-Santos
Feb 7, 2008·Fundamental & Clinical Pharmacology·Cristiano M ClementePedro J C Magalhães
Sep 29, 2011·Journal of Clinical Pharmacology·Charalambos VlachopoulosChristodoulos Stefanadis
Mar 10, 2010·Basic & Clinical Pharmacology & Toxicology·Riccardo LacchiniJose E Tanus-Santos
Dec 14, 2005·Toxicology·Jesus A VelhoAnibal E Vercesi
Nov 8, 2005·Nitric Oxide : Biology and Chemistry·Fernando BarbosaJose E Tanus-Santos
Oct 29, 2005·European Journal of Pharmacology·Allethea R Souza-SilvaJose E Tanus-Santos
Sep 29, 2011·European Journal of Pharmacology·Evandro M Neto-NevesJose E Tanus-Santos
Sep 17, 2014·Journal of Translational Medicine·Ananda T DiasElisardo C Vasquez
Nov 29, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Cesar A MeschiariJose E Tanus-Santos

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