Atrial fibrillation (AF) is the most common sustained arrhythmia. Pacemaker-like cells within cardiac muscle of the left atria that extend into the pulmonary vein (PV) to form a sleeve of cardiac muscle and are thought to contribute to the generation of ectopic beats that initiate and sustain AF (Haissaguerre et al., 1998). Noradrenaline (NA) which is a combined α-β adrenoreceptor agonist is known to induce ectopic activity in rat PV (Maupoil et al., 2007). Stretch is a main contributor to structural remodelling which opens stretch-activated ion channels (SACs) which enhances cellular Ca2+influx and Ca2+ release from sarcoplasmic reticulum. It is suggested that SACs may promote AF by causing Ca2+ overload (Bode et al., 2000). This study aimed to investigate the effect of stretch on NA induced ectopic activity of the rat PV. Male Sprague Dawley rats (180-300g) were euthanized, in accordance with the UK Home Office regulations, by cervical dislocation and their PVs carefully dissected and place in normal Tyrode solution, all experiments were carried out at 37oC. Action potentials (APs) were evoked at twice the threshold voltage, with a pulse duration of 2ms, at a frequency of 0.1Hz and stretched by applying 1g horizontal load, n = 5-6 for all experiments. Under resting conditions no ectopic APs were observed, with or without NA. Electrically evoked APs displayed the following characteristics at rest and in the presence of NA respectively: peak amplitude (PA) 99.18±2.66mV and 94.69±3.65mV; resting membrane potential (RMP) −80.56±3.11mV and −77.65+3.91mV; rise time (RT) 0.67±0.07ms and 0.71 ±0.1ms and action potential duration at 90% repolarization (APD90) 53.07±3.46ms and 51.60±4.34ms. Under stretch, the PV displayed some spontaneous activity, which had the following characteristics: PA 95.51±8.52mV, RMP −96.45±9.18mV, RT 0.6±0.06ms, APD90 59.58+2.11ms. Combining NA with a 1g stretch significantly (p<0.05) increased the frequency of ectopic activity by 10 fold compared with the stretching condition alone. The ectopic AP characteristics were: PA 97.18±1.37mV, RMP −98.09±7.96mV, RT 0.67±0.11ms, APD90 62.6±6.35ms. In PV with ectopic APs induced by NA plus stretch, gadolinium (Gd, 80μM) significantly (p<0.05) decreased the frequency of ectopic APs. In addition, Gd significantly increased APD90 by 41.18% compared to stretching plus NA. PA, RMP and RT were not significantly altered by Gd (p>0.05). These findings suggest that stretch can induce ectopic activity. However when combined with NA, ectopic activity significantly increased in the rat PV, which can be reduced by a SAC blocker. In conclusion, stretch may induce abnormal electrical activity in the PV through the action of stretch-activated ion channels, which is enhanced by NA. This stretch-induced arrhythmogenic activity may be involved in the generation of AF.