Arterial hypertension is an independent risk factor for atrial fibrillation (AF). The occurrence of AF is related to atrial dilation and extracellular matrix remodelling, shortening of atrial refractory period (AERP), and disturbed Ca2+ handling. In this study, we investigate if chronic hypertension in a porcine model induces structural and electrical changes in the atria, including Ca2+ homeostasis, and whether these changes enhance susceptibility to AF. To induce hypertension, 8 landrace pigs received subcutaneous DOCA-pellets (aldosterone analogon, 90-day release) and high-lipid/salt diet for 12 weeks. Eight weight-matched pigs served as controls. AERP was determined at different cycle lengths, S0, followed by a premature extrastimulus with 5 ms decrements. To test for AF susceptibility, a separate group of pigs (N=16) was instrumented with a telemetry-controlled pacemaker. Surgical procedures and in vivo interventions were performed under anesthesia (1.0 % isoflurane, 35 µg/kg/h fentanyl, 1 mg/kg/h midazolam, and 0.2 mg/kg/h pancouronium). A number of 5/16 pigs received DOCA/salt starting 2 weeks before the onset of rapid atrial pacing (600 bpm). After 2 weeks pacing, spontaneous atrial rhythm was monitored in unsedated pigs. AF susceptibility was defined as no detectable sinus rhythm for > 1h. Atrial myocytes were isolated from 12 w-treated DOCA (N=3) and control pigs (N=4), from left (LA) or right atrium (RA). Calcium transients (CaT) and cell shortening were measured during field stimulation using Fura-2 AM (0.5 – 2 Hz, 37°C). Data are expressed as mean ± s.e.m. After 12 w DOCA, systolic blood pressure was 139±11, vs 95±6 mmHg in control pigs (P<0.05, tail-cuff-method). LA area was enlarged (12.4±0.3 vs 9.7±0.6 cm2 in control, p<0.05, echocardiography). Interstitial fibrosis was reduced (14.8±1.8 vs 20.5±1.7% in control, p<0.05, expressed as % stained area by Sirius Red). AERP was significantly shortened in DOCA (fig 1). In single atrial myocytes, CaT amplitude was comparable in DOCA and control, in LA and RA. In LA, but not in RA, diastolic Ca2+ levels were lower (0.54±0.02 F340/380, n=5, N=1, vs 0.81±0.01 in control, n=7, N=2, 0.5 Hz), and Ca2+ decline was faster (RT50 81±24 ms, vs 197±21 ms in control, 0.5 Hz). While unchanged in RA, in LA cells, cell shortening was increased from 2.3±0.8% in control (n=3, N=2) to 5.4±0.5% in DOCA (n=8, N=1, 0.5 Hz). DOCA pigs were more susceptible to AF. After 2 w of rapid pacing, sustained AF (>1h) occurred in 4/5 DOCA pigs, vs 2/11 control pigs (p<0.05). In conclusion, although sinus rhythm is maintained, hypertensive pigs develop left atrial dilation and reduced electrical refractoriness, which was related to enhanced AF susceptibility. At the myocyte level, faster Ca2+ kinetics and increased contractility may reflect compensatory mechanisms that primarily occur in the left atria during chronic hypertension.