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
Panayiota PapadopoulosEdith Hamel

Abstract

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 contract...Continue Reading

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Citations

Jan 29, 2011·Acta Physiologica·C Lecrux, E Hamel
Sep 14, 2012·Immunopharmacology and Immunotoxicology·Gholamreza Azizi, Abbas Mirshafiey
Jul 9, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Panayiota PapadopoulosEdith Hamel
Apr 7, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nektaria Nicolakakis, Edith Hamel
Jun 28, 2018·Physiological Research·W LiA Ergul
Mar 1, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Abdelrahman Y FoudaAdviye Ergul

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