RESUMEN
Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg-1 nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.
Asunto(s)
Arginina/análogos & derivados , Endotelio Vascular/fisiopatología , Disfunción Eréctil/etiología , Lipoproteínas LDL/efectos adversos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Animales , Arginina/sangre , Modelos Animales de Enfermedad , Disfunción Eréctil/sangre , Disfunción Eréctil/fisiopatología , Hiperlipidemias/complicaciones , Lipoproteínas LDL/sangre , Masculino , Ratas Wistar , Factores de TiempoRESUMEN
Thiazolidinediones (TZDs) improve vascular endothelial dysfunction through non-genomic effects of peroxisomal proliferator-activated receptor γ. This study investigated the acute effect of one of the TZD, rosiglitazone, on endothelium-dependent relaxation response of corpus cavernosum (CC) in hypercholesterolemic rabbits. New Zealand rabbits were divided into two groups randomly as control and cholesterol groups. Hypercholesterolemia was induced by feeding rabbits with 2% cholesterol diet (w/w) for 6 weeks. Endothelium-dependent and -independent relaxation response of CC were evaluated in the presence of rosiglitazone by organ bath studies with cumulative doses of acetylcholine (Ach) and sodium nitroprusside (SNP). Maximal relaxation (Emax) response to Ach significantly decreased owing to hypercholesterolemia in CC tissues. However, in vitro incubation of rosiglitazone with different concentrations (0.1, 1 and 10 µm) did not improve the Ach-dependent Emax responses in hypercholesterolemic rabbit CC. Surprisingly, rosiglitazone caused a significant decrease in Ach-dependent relaxation in healthy CC. Emax responses to SNP did not differ in the presence of rosiglitazone in both the control and hypercholesterolemic groups. Rosiglitazone does not improve hypercholesterolemia-induced endothelial dysfunction in CC tissues while it dose-dependently impairs endothelium-dependent relaxation in healthy CC tissue.