Focus on Brain Angiotensin III and Aminopeptidase A in the Control of Hypertension

Table 2

Summary of investigations supporting a role for EC33 and PC18 (EC27) in blocking the release of vasopressin and controlling hypertension in animal models.

Preparation	Finding	Reference
Synthesis of EC33	Designed by Chauvel as a specific inhibitor of APA	[111]
	Synthesized by Reaux and colleagues
i.c.v. infusion-mice	EC33 increased the half-life of [^3H]AngII by 2.6 fold and blocked the formation of [^3H]AngIII	[108]
	PC18 and EC27 increased the half-life of [^3H]AngIII by 3.9 and 2.3 fold, respectively	[108, 111]
	EC33 reduced AngII-induced vasopressin release in a dose-response-dependent fashion	[111]
	Injection of PC18 and EC27 increased vasopressin release	[111]
Normotensive rats	Recorded from vasopressinergic neurons in the SON
(urethane-anesth.)	i.c.v. infusion of AngII and AngIII significantly increased firing rate. i.c.v. infusion of EC33 abruptly stopped firing rate for 4–6 min. i.c.v. infusion of AngII followed by EC33 prevented the increase in firing rate to AngII	[112]
i.c.v. infusion-SHRs	EC33 blocked AngII-induced pressor responses	[105, 113]
i.c.v. infusion-normotensive rats	EC33 blocked the pressor response induced by AngII and D-Asp^1AngII but had no effect on the pressor responses induced by AngIII or D-Arg^1AngIII. PC18 extended the duration of the D-Asp^1AngII-induced pressor response 2.5 fold, and the duration of the D-Arg^1 AngIII-induced pressor response by 10 to 15 fold. Pretreatment with Losartan blocked these pressor responses, indicating AT1 receptor involvement	[91]
Synthesis of RB150	Designed by Fournie-Zaluski	[107]
DOCA-salt rats	Intravenous administration of RB150 significantly reduced BP for 24 hours	[107]
	Oral administration of RB150 significantly reduced BP for 7 hours	[114, 115]