Chronic oral treatment with RB150 significantly decreased systolic blood pressure and plasma arginine vasopressin levels in hypertensive rats over 24 days.
Does chronic oral RB150 reduce systolic blood pressure in hypertensive deoxycorticosterone acetate-salt rats?
Chronic oral administration of the aminopeptidase A inhibitor prodrug RB150 significantly reduces systolic blood pressure and plasma arginine vasopressin levels in a rat model of salt-sensitive hypertension.
BACKGROUND AND OBJECTIVE: Hyperactivity of the brain renin-angiotensin (Ang) system has been implicated in the development and maintenance of hypertension. AngIII, one of the main effector peptides of the brain renin-Ang system, exerts a tonic stimulatory control over blood pressure (BP) in hypertensive rats. Aminopeptidase A (APA), the enzyme generating brain AngIII, represents a new therapeutic target for the treatment of hypertension. We developed RB150, a prodrug of the specific and selective APA inhibitor, EC33. When given orally in acute treatment in hypertensive rats, RB150 crosses the gastrointestinal and blood-brain barriers, enters the brain, inhibits brain APA activity and decreases BP. We investigate, here, the antihypertensive effects of chronic oral RB150 (50 mg/kg per day) treatment over 24 days in alert hypertensive deoxycorticosterone acetate-salt rats. METHODS: We measured variations in Brain APA enzymatic activity, SBP, plasma arginine vasopressin levels and metabolic parameters after RB150 chronic administration. RESULTS: This resulted in a significant decrease in SBP over the 24-day treatment period showing that no tolerance to the antihypertensive RB150 effect was observed throughout the treatment period. Chronic RB150 treatment also significantly decreased plasma arginine vasopressin levels and increased diuresis, which participate to BP decrease by reducing the size of fluid compartment. Interestingly, we observed an increased natriuresis without modifying both plasma sodium and potassium levels. CONCLUSION: Our results strengthen the interest of developing RB150 as a novel central-acting antihypertensive agent and evaluating its efficacy in salt-sensitive hypertension.
Marc et al. (Fri,) conducted a other in Hypertension. RB150 was evaluated on Systolic blood pressure (SBP). Chronic oral treatment with RB150 significantly decreased systolic blood pressure and plasma arginine vasopressin levels in hypertensive rats over 24 days.