NDLI: Chronic ET(A) receptor blockade prevents endothelial dysfunction of small arteries in apolipoprotein E-deficient mice.

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Chronic ET(A) receptor blockade prevents endothelial dysfunction of small arteries in apolipoprotein E-deficient mice.

Content Provider	Semantic Scholar
Author	D'uscio, Livius V. Barton, Matthias Shaw, Sidney Lüscher, Thomas F.
Copyright Year	2002
Abstract	OBJECTIVE This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ET(A) receptor antagonist. METHODS ApoE-deficient and C57BL/6J control mice were fed for 30 weeks with normal chow or high-fat Western-type diet alone or in combination with darusentan (LU135252; 50 mg/kg/day). Vasomotor reactivity of isolated small mesenteric arteries (I.D. 200-250 microm) was studied in vitro under perfused and pressurized conditions. RESULTS In both mouse strains, about one fourth of the endothelium-dependent relaxant response to acetylcholine was insensitive to inhibition by L-NAME and indomethacin. In mesenteric arteries of apoE-deficient mice on Western-type diet, increased intima-media thickness and levels of endothelin-1 protein were observed. In addition, NO-mediated endothelium-dependent relaxation to acetylcholine was reduced without affecting L-NAME/indomethacin insensitive relaxation and contractions to endothelin-1 and serotonin were enhanced. Treatment with darusentan normalized vascular structure, NO-mediated relaxation to acetylcholine and contractions to endothelin-1 and serotonin without affecting blood pressure or plasma cholesterol levels. CONCLUSIONS Severe hypercholesterolemia in apoE-deficient mice is associated with attenuation of NO-mediated relaxation to acetylcholine and increased vascular endothelin-1 content. Chronic ET(A) receptor blockade may provide a new therapeutic approach to improve NO-mediated endothelium-dependent vasomotion in small arteries.
File Format	PDF HTM / HTML
PubMed reference number	11827700
Journal	Medline
Volume Number	53
Issue Number	2
Alternate Webpage(s)	http://doc.rero.ch/record/303649/files/53-2-487.pdf
Journal	Cardiovascular research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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