a-192621 and Alzheimer-Disease

a-192621 has been researched along with Alzheimer-Disease* in 1 studies

Other Studies

1 other study(ies) available for a-192621 and Alzheimer-Disease

ArticleYear
Selective in vivo antagonism of endothelin receptors in transforming growth factor-beta1 transgenic mice that mimic the vascular pathology of Alzheimer's disease.
    Canadian journal of physiology and pharmacology, 2010, Volume: 88, Issue:6

    Increased levels of transforming growth factor-beta1 (TGF-beta1) induce a vascular pathology that shares similarities with that seen in Alzheimer's disease, and which possibly contributes to the cognitive decline. In aged transgenic mice that overexpress TGF-beta1 (TGF mice), we previously found reduced dilatory function and selectively impaired endothelin-1 (ET-1)-induced contraction. Here we studied the effects of chronic treatments with selective ETA (ABT-627) or ETB (A-192621) receptor antagonist on cerebrovascular reactivity, cerebral perfusion, or memory performance. The dilatory deficit of TGF mice was not improved by either treatment, but both ET-1 contraction and basal nitric oxide (NO) production were distinctly altered. Although ABT-627 was devoid of any effect in TGF mice, it virtually abolished the ET-1-induced contraction and NO release in wild-type (WT) littermates. In contrast, A-192621 only acted upon TGF mice with full recovery of ET-1 contraction and baseline NO synthesis. TGF mice, treated or not, had no cognitive deficit in the Morris water maze, nor did ABT-627-treated WT controls despite severely impaired vasoreactivity. These findings confirm that ETA receptors primarily mediate the ET-1-induced contraction. Further, they suggest that ETB receptors play a detrimental role in conditions of increased TGF-beta1 and that vascular dysfunction does not inevitably lead to cognitive deficit.

    Topics: Aging; Alzheimer Disease; Animals; Atrasentan; Blood Vessels; Brain; Cerebral Arteries; Cerebrovascular Circulation; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin Receptor Antagonists; Endothelin-1; Female; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nitric Oxide; Nitroarginine; Pyrrolidines; Transforming Growth Factor beta1; Vasoconstriction; Vasodilation; Vasodilator Agents; Vibrissae

2010