Abstract 18208: Vasomera™, a Novel VPAC2-selective Vasoactive Intestinal Peptide Agonist, Triggers Sustained Blood Pressure Control in Telemetered Spontaneously Hypertensive Rats: Additive Effects to Atenolol, Amlodipine, and Ramipril
The natural vasoactive intestinal peptide (VIP) triggers potent vasodilatation by activating the G-protein-coupled VPAC1 and VPAC2 receptors; however, VIP's clinical utility is limited due to its short half-life and VPAC1-mediated side-effects. Vasomera™ is a novel long-acting biopolymer-based selective VPAC2-receptor agonist. Here, the hemodynamic effects of Vasomera when given as a single-dose SQ bolus to conscious spontaneously hypertensive rats (SHR) pretreated with three common anti-hypertensives were tested. SHR rats (351 ± 4 g, n = 8) were instrumented for telemetric blood pressure and ECG monitoring. First, Vasomera (9 mg [177nmol]/kg, SQ) and placebo (VEH) were assayed in untreated animals. Then, the effects of Vasomera were tested during concomitant oral β-AR blockade (+BB, atenolol 20 mg/kg/day), calcium-channel blockade (+CCB, amlodipine 5 mg/kg/day) and ACE-inhibition (+ACE, ramipril 1 mg/kg/day). Mean pressure (MAP) and heart rate (HR) were measured/averaged over 24hrs both pre and post-dosing. Vasomera induced blood pressure decreases that were sustained for up to 12hrs post-dosing (see Fig. A). On average, Vasomera lowered MAP by 9 ± 1 % (188 ± 6 to 171 ± 5 mmHg, P < 0.05). Vasomera's vaso-relaxation was preserved/enhanced in rats pre-treated with either atenolol (-14 ± 1%, P < 0.05), amlodipine (-13 ± 2%, P < 0.05), and/or ramipril (-9 ± 2%, P < 0.05) (see Fig. B). Vasomera triggered moderate cardio-acceleration in untreated rats (+8 ± 1%, 355 ± 6 to 384 ± 8 bpm, P < 0.05); such chronotropy was blunted under β-AR blockade (+6 ± 1%, 278 ± 2 to 294 ± 2 bpm), but was unaffected by amlodipine or ramipril (see Fig. C). In all cases, heart rates were lower than in controls, and no adverse clinical effects were noted. Vasomera, a novel VPAC2 agonist, can provide long-acting blood pressure control synergistically with concomitant anti-hypertensive therapies (e.g., β-AR blockade) and may represent a novel adjunct therapy for resistant/uncontrolled hypertension.
- © 2011 by American Heart Association, Inc.