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Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms.
Eur J Pharmacol. 2004 Sep 13; 498(1-3):189-94.EJ

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 suggest that atorvastatin increases the vascular sensitivity to sildenafil through NO-mediated mechanisms.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, Brazil, 14049-900.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15363994

Citation

Castro, Michele M., et al. "Atorvastatin Enhances Sildenafil-induced Vasodilation Through Nitric Oxide-mediated Mechanisms." European Journal of Pharmacology, vol. 498, no. 1-3, 2004, pp. 189-94.
Castro MM, Rizzi E, Rascado RR, et al. Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms. Eur J Pharmacol. 2004;498(1-3):189-94.
Castro, M. M., Rizzi, E., Rascado, R. R., Nagassaki, S., Bendhack, L. M., & Tanus-Santos, J. E. (2004). Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms. European Journal of Pharmacology, 498(1-3), 189-94.
Castro MM, et al. Atorvastatin Enhances Sildenafil-induced Vasodilation Through Nitric Oxide-mediated Mechanisms. Eur J Pharmacol. 2004 Sep 13;498(1-3):189-94. PubMed PMID: 15363994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin enhances sildenafil-induced vasodilation through nitric oxide-mediated mechanisms. AU - Castro,Michele M, AU - Rizzi,Elen, AU - Rascado,Ricardo R, AU - Nagassaki,Sabrina, AU - Bendhack,Lusiane M, AU - Tanus-Santos,Jose E, PY - 2004/04/26/received PY - 2004/07/01/revised PY - 2004/07/06/accepted PY - 2004/9/15/pubmed PY - 2005/3/1/medline PY - 2004/9/15/entrez SP - 189 EP - 94 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 498 IS - 1-3 N2 - 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 suggest that atorvastatin increases the vascular sensitivity to sildenafil through NO-mediated mechanisms. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15363994/Atorvastatin_enhances_sildenafil_induced_vasodilation_through_nitric_oxide_mediated_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(04)00762-9 DB - PRIME DP - Unbound Medicine ER -