Abstract 632: Vasomera, a Novel VPAC2-Selective Vasoactive Intestinal Peptide Agonist, Improves Arterial Elastance and Ventriculo-Arterial Coupling in Rats with Induced Diastolic Dysfunction via Renoprival Hypertension
Vasomera™ is a first-in-class stable long-acting vasoactive intestinal peptide (VIP) agonist, with preferential actions on the G-protein-coupled VPAC2-receptors; VIP mediates cardiopulmonary regulation and has been proposed as a therapeutic target for both hypertension and systolic dysfunction. Here, the acute effects of Vasomera in load-independent function and ventriculo-arterial coupling were in evaluated in a rats with chronic diastolic dysfunction, mimicking heart failure with preserved ejection fraction (HFpEF).
Diastolic dysfunction, as demonstrated by altered E/A ratios via echocardiography, was induced by renoprival hypertension secondary to renal wrapping (RW). Conditioned rats (n = 5) were instrumented for the determination of left-ventricular (LV) hemodynamics as well as load-independent fnction and ventriculo-arterial coupling (via pressure-volume relationships); data were evaluated before/after a single-dose continuous IV infusion of Vasomera (7.5 μg/kg/min IV).
Vasomera decreased the estimated arterial elastance (Ea: -20 ± 5%, P < 0.05) with negligible changes in heart rate (-4 ± 2%). Improved inotropy (Ees: +28 ± 8% and PRSW: +22 ± 3%, P < 0.05) was observed post-treatment, suggesting improved ventriculo-arterial coupling (Ea/Ees: -37 ± 5%, P < 0.05). Concomitantly, Vasomera reduced filling pressures (EDP: -30 ± 8%, P < 0.05), accelerated the time-constant of relaxation (tau: -24 ± 3%, P < 0.05) and improved compliance (EDPVR: -26 ± 5%, P < 0.05).
Vasomera, a novel VPAC2 agonist, improved arterial elastance and ventriculo-arterial coupling, while improving indices of diastolic function (i.e., lusitropy) in animals with chronic renoprival hypertension mimicking HFpEF.
Author Disclosures: C.L. del Rio: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Modest; PhaseBio. G. Consultant/Advisory Board; Modest; PhaseBio. Y. Ueyama: None. L. Georgopoulos: A. Employment; Significant; PhaseBio. S. Arnold: A. Employment; Significant; PhaseBio. R.L. Hamlin: G. Consultant/Advisory Board; Modest; QTest Labs.
- © 2014 by American Heart Association, Inc.