Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice.
BACKGROUND
The 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.


METHODS
Twenty 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 x 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.


RESULTS
ACh-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.


CONCLUSIONS
These 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.
Cola
Maine S
MS
Laboratory of Transgenes and Cardiovascular Control, Physiological Sciences Graduate Program, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Gava
Agata L
AL
Meyrelles
Silvana S
SS
Vasquez
Elisardo C
EC
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006937:Hypercholesterolemia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D013152:Splanchnic Circulation; D014655:Vascular Resistance
D001057:Apolipoproteins E