Effects of β-sheet breaker peptides on altered responses of thoracic aorta in rats' Alzheimer's disease model induced by intraamygdaloid Aβ40.

AIMS

Alzheimer's disease (AD) is characterized by vascular dysfunction, in addition to memory impairment. Previously we found that β-sheet breaker peptides (βSBPs) improved memory impairment induced by amyloid β-peptide Aβ40. In this study we investigated βSBP effects on vascular responses in a rat model of AD.

MAIN METHODS

AD model was induced by bilateral injection of aged Aβ40 (3 nmol) into the amygdala. βSBPs 15-22, 16-23 and 17-24 (30 nmol) were injected into the amygdala 8 days after Aβ40. The Aβ40 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 Aβ40.

KEY FINDINGS

Aβ40 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 Aβ40, an effect reduced by βSBPs 15-22 and 16-23. In denuded aorta, Aβ40 decreased PE-contractility. βSBP15-22 increased ACh-relaxation, whereas βSBP17-24 increased K(+)-contraction. Aβ40 decreased NO, an effect inhibited by the βSBP15-22.

SIGNIFICANCE

These results provide evidence that Aβ40-perverted endothelium-dependent relaxation and decreased serum NO in AD rats were improved differentially by the βSBP15-22. These results show the ability of Aβ40 to alter vascular responses. βSBPs appear to be promising candidate for prevention of these consequences and therapy of AD.