The sympathetic nervous system and adrenomedullin (AM) both participate in the regulation of cardiac and circulatory function but their interaction remains uncertain. We have examined the effects of AM on cardiac sympathetic nerve activity (CSNA) and hemodynamics and contrasted these effects with pressure-matched nitro-prusside (NP) administration in normal conscious sheep. Compared with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but the rise with AM was significantly greater than that induced by NP (P<0.001). Cardiac output increased in response to AM compared with both control and NP (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant differences between any treatment day. In conclusion, we have demonstrated that AM is associated with a greater increase in CSNA and heart rate for a given change in arterial pressure than seen with the classic balanced vasodilator NP.