Intravascular beta-amyloid infusion increases blood pressure: implications for a vasoactive role of beta-amyloid in the pathogenesis of Alzheimer's disease.
Hypertension has been recognized as a risk factor for Alzheimer's disease (AD). Moreover, serum beta-amyloid (A beta) levels are elevated in several mutations linked to familial AD, as well as in some sporadic AD individuals. To determine the in vivo effects of A beta on blood pressure, A beta(1-40) was infused intra-arterially into anesthetized rats. For all animals, strong correlations exist between pre-infusion mean arterial blood pressure (MA beta) and post-arterial infusion increases in blood pressure. In spontaneously hypotensive animals, A beta infusion resulted in substantial increases in MA beta compared to vehicle distilled water infusion. A beta(1-40) was also able to accelerate MA beta return from induced hypotension, but infusion of A beta(1-42), or rat amylin had no such effect. These results provide evidence that circulating A beta(1-40) can exert vasopressor actions in vivo. Moreover, they suggest a pathophysiologic role for vascular A beta in AD that precedes A beta deposition and dementia onset.
Department of Biology, University of South Florida, Tampa 33620, USA.
G W
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Arendash
G C
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Su
F C
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Crawford
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KB
Bjugstad
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Mullan
D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D007261:Infusions, Intra-Arterial; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D014662:Vasoconstrictor Agents