OBJECTIVETo explore the mechanism underlying changes in microvascular reactivity in single- and double-transgenic mice.

METHODSPeripheral vascular reactivity to the vasodilators, acetylcholine and sodium nitroprusside, on perfused microvasculature of the hind footpad was investigated using nontransgenic mice, single-transgenic mice expressing the human APP-C100 (TgC100. WT or TgC100. V717F) and double-transgenic mice coexpressing human APP-C100 and human SOD(1) (G93A) genes.

RESULTSSingle TgC100 and double Tg mice C100/SOD(1) (G93A) at 2 - 3 months old showed a statistical decrease of 28% in blood flux compared to nontransgenic control mice. In addition, vasodilative responsiveness was markedly reduced to 34% in 8 - 9 months old TgC100 mice compared to control mice. There was no significant difference in the profile of vasodilative reaction between TgC100. WT and TgC100. V717F mice. TgC100 and double Tg mice also had higher levels of A beta peptide in plasma than nontransgenic mice (P < 0.01).

CONCLUSIONSThe present study suggests that the altered reactivity of the microvasculature may be mediated by circulating soluble A beta peptides. The mechanisms underlying the vasoactivity of circulating A beta in TgC100 and double Tg mice may involve both the endothelium and nonendothelium.

Acetylcholine ; pharmacology ; Amyloid beta-Peptides ; blood ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Blood Flow Velocity ; drug effects ; Hindlimb ; blood supply ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Mutation ; Nitroprusside ; pharmacology ; Peptide Fragments ; blood ; Superoxide Dismutase ; genetics ; metabolism ; Vasodilator Agents ; pharmacology