Elevated renal sympathetic nerve activity (RSNA) in heart failure is correlated with poor outcome, but little is known about what triggers the increase in sympathetic tone or indeed at what stage the increased occurs. While males are more likely to experience myocardial infarction (MI) than females, females often have a worse prognosis. Interestingly females are also less likely to be prescribed beta-blockers. The aim of this project was to determine if there are gender differences in the RSNA response immediately following a myocardial infarct (MI). The University of Auckland Animal Ethics Committee approved all experiments. Male and female Wistar rats were anaesthetised with urethane (1000-1500 mg/kg I.P) and α-chloralose (80-120 mg/kg I.P). Rats were intubated and ventilated. The left renal artery was exposed and the renal nerves dissected for recording of RSNA along with arterial pressure (femoral artery) and ECG. A left intercostal thoracotomy was performed to expose the heart, the pericardium was removed. After a one hour period of baseline recording the left coronary artery was ligated using a 6-0 suture. In the sham group the chest was opened, pericardium removed, a suture inserted around the coronary artery but not tied. In male rats (n=7) coronary ligation resulted in abrupt increase (32 ± 12%, mean+sem) in RSNA before subsiding to lower steady state within 10 minutes of the infarct for the next 2 hours (13 ± 4 % above the baseline level, P < 0.05, ANOVA). In contrast in female rats (n=7) no significant changes in RSNA were observed in response to myocardial infarction. No change in RSNA was observed in sham operated rats (n=10). Arterial pressure responses were also different between the male and female rats; two hours post-infarct arterial pressure was 10 ± 5mmHg below that seen in the sham group (P < 0.05), whereas arterial pressure in the male rats was not significantly different to the shams. Baseline baroreflex control of RSNA differed between the sexes with the females displaying a significantly reduced maximum RSNA response to decreases in mean arterial pressure compared to males (64±7% vs. 89±6%, P>0.05). In both the males and females, neither sham surgery nor myocardial infarction had a significant effect on baroreflex control over heart rate or RSNA at 60min after of the intervention. Animals were humanely killed with euthatal at the end of these studies. Post-mortem analysis showed the coronary ligation resulted in a non-perfused area of left ventricle of 35-50%. These results indicate that gender exerts a major influence on the resulting sympathoactivation occurring after MI. We suggest that different treatment strategies may justified based on gender after MI.