Antiarrhythmic Effects of Vasostatin‐1. Background: We examined the antiarrhythmic effects of vasostatin‐1, a recently identified cardioregulatory peptide, in canine models of atrial fibrillation (AF).Methods and Results: In 13 pentobarbital‐anesthetized dogs bilateral thoracotomies allowed the attachment of multielectrode catheters to superior and inferior pulmonary veins and atrial appendages (AA). Rapid atrial pacing (RAP) was maintained for 6 hours. Each hour, programmed stimulation was performed to determine the window of vulnerability (WOV), a measure of AF inducibility, at all sites. During the last 3 hours, vasostatin‐1, 33 nM, was injected into the anterior right (AR) ganglionated plexus (GP) and inferior right (IR) GP every 30 minutes (n = 6). Seven dogs underwent 6 hours of RAP only (controls). At baseline, acetylcholine, 100 mM, was applied on the right AA and AF duration was recorded before and after injection of vasostatin‐1, 33 nM, into the ARGP and IRGP. In separate experiments (n = 8), voltage–sinus rate response curves (surrogate for GP function) were constructed by applying high‐frequency stimulation to the ARGP with incremental voltages with or without vasostatin‐1. Vasostatin‐1 significantly decreased the duration of acetylcholine‐induced AF (11.0 ± 4.1 vs 5.5 ± 2.6 min, P = 0.02). The cumulative WOV (the sum of individual WOVs) significantly increased (P < 0.0001) during the first 3 hours and decreased toward baseline in the presence of vasostatin‐1 (P < 0.0001). Cumulative WOV in controls steadily increased. Vasostatin‐1 blunted the slowing of sinus rate with increasing stimulation voltage of ARGP.Conclusions: Vasostatin‐1 suppresses AF inducibility, likely by inhibiting GP function. These data may provide new insights into the role of peptide neuromodulators for AF therapy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 771‐777, July 2012)