Intravascular β-amyloid infusion increases blood pressure:: implications for a vasoactive role of β-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 (MAP) and post-arterial infusion increases in blood pressure. In spontaneously hypotensive animals, A beta infusion resulted in substantial increases in MAP compared to vehicle distilled water infusion. A beta(1-40) was also able to accelerate MAP 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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.