Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice
Braz. j. med. biol. res
; 42(12): 1191-1195, Dec. 2009. ilus
Article
em En
| LILACS
| ID: lil-532304
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ABSTRACT
The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response 51 ± 8 vs 53 ± 5 percent, respectively) and SNP-induced vasorelaxation (maximal response 73 ± 6 vs 74 ± 6 percent, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm² x 10³). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.
Palavras-chave
Texto completo:
1
Índice:
LILACS
Assunto principal:
Apolipoproteínas E
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Resistência Vascular
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Endotélio Vascular
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Sirolimo
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Aterosclerose
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Imunossupressores
Limite:
Animals
Idioma:
En
Revista:
Braz. j. med. biol. res
Assunto da revista:
BIOLOGIA
/
MEDICINA
Ano de publicação:
2009
Tipo de documento:
Article