Effects of aminopeptidase inhibition on the half-lives of [ 125I]angiotensins in the cerebroventricles of the rat

Abstract

Anesthetized Sprague-Dawley rats fitted with intracerebroventricular (i.c.v.) cannulas were infused with one of the aminopeptidase inhibitors, amastatin or bestatin, over a 5-min period. After infusion, 1–2 × 10 6 cpm of [ 125I]angiotensin II([ 125I]AII) or [ 125I]angiotensin III([ 125AIII) was injected through the same cannula. The rats were subsequently killed 60 s later by focused microwave irradiation which instantaneously terminated further [ 125I]angiotensin metabolism. HPLC analysis of the extracted [ 125I]angiotensin and metabolic products allowed for the calculation of t 1 2 s of disappearance for the parent peptides. Both inhibitors effectively lengthened the half-lives of [ 125I]AII and [ 125I]AIII. Bestatin, which is considered a selective aminopeptidase B blocker, had a more pronounced effect on [ 125I]AIII metabolism, while amastatin, a selective aminopeptidase A inhibitor, was better at slowing [ 125I]AII degradation. The results indicate that amastatin and bestatin are very effective blockers of the cerebroventricular metabolism of angiotensins but are only marginally selective with regard to AII and AIII.