In order to clarify the hypotensive mechanisms of alpha-human atrial natriuretic polypeptide (alpha-hANP), hemodynamic responses were investigated in anesthetized rats. Mean blood pressure (MBP), cardiac index (CI) and total peripheral resistance index (TPRI) were measured before and after infusion of alpha-hANP (30 ng/min per 100 g body weight) in intact, nephrectomized, atropinized or chemically sympathectomized rats. MBP was significantly reduced in all rats, associated with a decrease in CI. TRPI decreased slightly in sympathectomized rats but was unchanged in the other rats. The alpha-hANP-induced reduction in MBP of sympathectomized rats was significantly less than that of intact rats (9.5 +/- 1.2 vs. 20.9 +/- 2.6%; P less than 0.01). Similarly, the decrease in CI of sympathectomized rats was significantly less than that of intact rats (5.0 +/- 1.8 vs. 21.7 +/- 5.3%; P less than 0.05). Changes in MBP and CI of nephrectomized, atropinized or intact rats did not differ significantly. It is suggested that neither fluid loss nor parasympathetic nerves play an important role in the acute hemodynamic response. However, sympathetic nerves might be involved in the cardiosuppressive action of alpha-hANP.