Abstract
BackgroundThe effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57) and hypercholesterolemic (ApoE) female mice in both normal and ovariectomized conditions.MethodsTwenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10-9 to 2 × 10-3 mol/L), acetylcholine (ACh) and sodium nitroprusside (SNP) (10-10 to 10-3 mol/L) were evaluated in the isolated mesenteric arteriolar bed through dose-response curves.ResultsACh-induced relaxation was significantly reduced (P < 0.05) in ApoE compared with 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 ACh-induced relaxation in the C57 group (maximal response: 61 ± 4%) but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 ± 5%). SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice.ConclusionThese data show an impairment of endothelial function in the 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 endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.
Highlights
The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear
Considering that the responsiveness of resistance vessels is still poorly understood in the mouse and that there are few studies in atherosclerotic female mice, the present study was designed to evaluate endothelial function in the isolated mesenteric arteriolar bed of C57BL/6 and ApoE-deficient mice under both normal and ovariectomy conditions
Body weight was not altered; uterus weight was significantly reduced in ovariectomized groups, with no differences between C57 and ApoE animals
Summary
The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE) mice, a murine model of spontaneous atherosclerosis, are still unclear. The murine model that lacks the gene encoding apolipoprotein E (ApoE) and spontaneously develops hypercholesterolemia and atherosclerotic lesions similar to those found in human beings [2,3] has greatly contributed to the understanding of this disease. In this animal, on a chow diet, as early as 10 weeks of age, monocyte adhesions are observed, followed by intermediate lesions containing foam and smooth muscle cells at 15 weeks and sequentially by fibrous plaques at 20 weeks of age [4]. Considering that the responsiveness of resistance vessels is still poorly understood in the mouse and that there are few studies in atherosclerotic female mice, the present study was designed to evaluate endothelial function in the isolated mesenteric arteriolar bed of C57BL/6 and ApoE-deficient mice under both normal and ovariectomy conditions
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