RESUMO
To assess the antioxidant effects of atorvastatin (atorva) on dexamethasone (dex)-induced hypertension, 60 male Sprague-Dawley rats were treated with atorva 30 mg/kg/day or tap water for 15 days. Dex increased systolic blood pressure (SBP) from 109 +/- 1.8 to 135 +/- 0.6 mmHg and plasma superoxide (5711 +/- 284.9 saline, 7931 +/- 392.8 U/ml dex, P < 0.001). In this prevention study, SBP in the atorva + dex group was increased from 115 +/- 0.4 to 124 +/- 1.5 mmHg, but this was significantly lower than in the dex-only group (P' < 0.05). Atorva reversed dex-induced hypertension (129 +/- 0.6 mmHg, vs. 135 +/- 0.6 mmHg P' < 0.05) and decreased plasma superoxide (7931 +/- 392.8 dex, 1187 +/- 441.2 atorva + dex, P < 0.0001). Plasma nitrate/nitrite (NOx) was decreased in dex-treated rats compared to saline-treated rats (11.2 +/- 1.08 microm, 15.3 +/- 1.17 microm, respectively, P < 0.05). Atorva affected neither plasma NOx nor thymus weight. Thus, atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat.
Assuntos
Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Pirróis/farmacologia , Análise de Variância , Animais , Atorvastatina , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Masculino , Nitratos/sangue , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Nitritos/sangue , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxidos/sangue , Timo/anatomia & histologiaRESUMO
1. Adrenocorticotropic hormone (ACTH)-induced hypertension is associated with nitric oxide (NO) deficiency and increased oxidative stress. Atorvastatin (Ato), an HMG-Co-enzyme-A reductase inhibitor has been reported to enhance availability of NO. The aim of the study was to assess whether pretreatment with Ato would prevent the development of ACTH-induced hypertension and whether established ACTH-induced hypertension could be reversed with subsequent administration of Ato in rats. 2. Male Sprague-Dawley rats (n = 60) were treated with Ato (30 mg/kg per day in drinking water) or tap water for 15 days. ACTH (0.2 mg/kg per day s.c) or saline was started 4 days after Ato treatment or non-treated rats and continued for 11-13 days (prevention study). In the reversal study, Ato was given on day 8 of ACTH/Saline treatment for 5 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. 3. Adrenocorticotropic hormone treatment increased SBP (110 +/- 2-136 +/- 2 mmHg, P < 0.001) and aortic superoxide production (P < 0.001). Ato alone did not alter SBP, but Ato pretreatment prevented ACTH-induced hypertension compared with that in rats treated with ACTH alone (118 +/- 2 and 136 +/- 2 mmHg, respectively, P cent < 0.01). Ato partially reversed ACTH-induced hypertension (124 +/- 3 and 136 +/- 2 mmHg, respectively, P cent < 0.05). Plasma nitrate/nitrite (NOx) was decreased in ACTH-treated rats compared with saline treated rats (6.6 +/- 0.4 saline and 4.5 +/- 0.5 micromol/L ACTH, P < 0.001). Atorvastatin affected neither plasma NOx nor aortic superoxide production. 4. Atorvastatin prevented and partially reversed ACTH-induced hypertension in the rat.