Effects of ß-sheet breaker peptides on altered responses of thoracic aorta in rats' Alzheimer's disease model induced by intraamygdaloid Aß40

Abstract

Aims Alzheimer's disease (AD) is characterized by vascular dysfunction, in addition to memory impairment. Previously we found that ß-sheet breaker peptides (ßSBPs) improved memory impairment induced by amyloid ß-peptide Aß40. In this study we investigated ßSBP effects on vascular responses in a rat model of AD. Main methods AD model was induced by bilateral injection of aged Aß40 (3 nmol) into the amygdala. ßSBPs 15-22, 16-23 and 17-24 (30 nmol) were injected into the amygdala 8 days after Aß40. The Aß40 deposits were examined immunohistochemically in cerebral vessels and thoracic aorta. The effects on high-K+ contractility, phenylephrine (PE) contractility, acetylcholine (ACh) relaxation and sodium nitroprusside (SNP) relaxation were investigated in isolated thoracic aorta. Nitric oxide (NO) level in serum was investigated 14 days after Aß40. Key findings Aß40 was localized and it induced vascular damage in minute and small perforating cerebral vascular endothelium, and tunica intima (endothelial) and media (smooth muscle cells) of the thoracic aorta. In intact aorta, ACh-relaxation was decreased by Aß40, an effect reduced by ßSBPs 15-22 and 16-23. In denuded aorta, Aß40 decreased PE-contractility. ßSBP15-22 increased ACh-relaxation, whereas ßSBP17-24 increased K+-contraction. Aß40 decreased NO, an effect inhibited by the ßSBP15-22. Significance These results provide evidence that Aß40-perverted endothelium-dependent relaxation and decreased serum NO in AD rats were improved differentially by the ßSBP15-22. These results show the ability of Aß40 to alter vascular responses. ßSBPs appear to be promising candidate for prevention of these consequences and therapy of AD. © 2013 Elsevier Inc.