Intravascular beta-amyloid infusion increases blood pressure: implicationsfor 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 m utations 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, stro ng correlations exist between pre-infusion mean arterial blood pressure (MA P) 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 abl e 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 th at circulating A beta(1-40) can exert vasopressor actions in vivo. Moreover , they suggest a pathophysiologic role for vascular A beta in AD that prece des A beta deposition and dementia onset. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.