Manipulation of aminopeptidase activities: differential effects on iontophoretically applied angiotensins in rat...

During a recent comparison of iontophoretically applied angiotensin II (ANG II) and angiotensin III (ANG III) in the paraventricular nucleus of the rat we observed that ANG III was more potent than ANG II. This suggested that ANG II may have to be converted to ANG III before it becomes active. To test this hypothesis we performed two experiments. Firstly, we examined the effects of bestatin, an aminopeptidase B inhibitor, on the activity of applied ANG II and ANG III. Next, we monitored the effects of amastatin, a specific aminopeptidase A inhibitor, on the action of coapplied ANG II or ANG III. Bestatin, while having no activity of its own, dramatically enhanced the actions of both ANG II and ANG III. Amastatin, on the other hand, had little effect on ANG III's action and diminished or totally blocked ANG II-dependent activity. Like bestatin, amastatin had no effects alone. In total these results strongly support the notion that ANG II must be converted to ANG III in the brain before it is activated.