Avaliação da função endotelial de camundongos hipercolesterolêmicos fêmeas
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Data
2009-09-11
Autores
Cola, Maíne Sousa
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Universidade Federal do Espírito Santo
Resumo
The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still controversial. The studies were mostly made on conductance vessels and they indicate that females are more susceptible than males to endothelial dysfunction. In the present study we evaluated the endothelium function of resistance vessels from normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice in both normal and ovariectomy conditions. Five month-old C57 and ApoE mice underwent ovariectomy (OVX) or sham surgery and were studied 30 days later. The vascular reactivity to norepinephrine (NE, 10-9 to 2x10-3 mol/L), acetylcholine (ACh, 10-10 to 10-3 mol/L) and sodium nitroprusside (SNP, 10-10 to 10-3 mol/L) was evaluated in the isolated mesenteric arteriolar bed through concentrationeffect curves. ACh-induced relaxation was significantly reduced in ApoE compared to C57 animals, as indicated by both the maximal response (37±4% vs. 72±1%) and the LogEC50 (5.67 ± 0.18 vs. 6.23 ± 0.09 mol/L). Ovariectomy caused a significant impairment in the ACh-induced relaxation in the C57 group (maximal response: 61 ± 4%) but did not worse the deficient state of relaxation of ApoE animals (maximal response: 39 ± 5%). SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice. This is the first study to show an impairment of endothelial function in resistance vessels of spontaneously atherosclerotic (ApoE-deficient) female mice compared with normal (C57) female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired the endothelial function in C57, did not cause additional damage in ApoE-deficient mice.