Preservation of the arterial baroreflex response is important to restore cardiac output and blood pressure by reflex sympathetic nerve activation in the event of sudden hypotension caused by acute blood loss during surgery. However, the arterial baroreflex may be significantly attenuated by both anesthetics and hypotensive agents. In isoflurane-anesthetized dogs, the authors investigated the arterial baroreflex response 1) to bolus injections of sodium nitroprusside (SNP), prostaglandin E1 (PGE1) and trimethaphan (TM); and 2) to rapid blood loss (5 ml/kg) before and during induced hypotension with SNP, PGE1, and TM by measuring mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). Hypotension produced by both SNP and PGE1 was accompanied by an increase in RSNA and HR. The increase in RSNA and HR following the SNP bolus injection was significantly greater than that following injection of PGE1 (P < 0.05). Trimethaphan was associated with a decrease in RSNA and HR. Rapid blood loss resulted in the same degree of MAP reduction (20 .+-. 2 mmHg) before and during induced hypotension. Sensitivities of baroreflex, as evaluated by ratios of maximum changes in RSNA or HR to MAP (.DELTA.RSNA/.DELTA.MAP, .DELTA.HR/.DELTA.MAP), in response to rapid blood loss, were significantly suppressed during continuously induced hypotension, as compared with responses before induced hypotension. Despite the same degree of induced hypotension (70 .+-. 5 mmHg of MAP), .DELTA.RSNA/.DELTA.MAP and .DELTA.HR/.DELTA.MAP in response to rapid blood loss were significantly greater with PGE1 than those with SNP (P < 0.05). Because of its sympathetic ganglion blocking action, arterial baroreflex sensitivity was suppressed by rapid blood loss during TM infusion. The authors conclude that induced hypotension with PGE1 provides a greater margin of safety than that associated with SNP when acute blood loss occurs during isoflurane anesthesia. Trimethaphan is inferior to both PGE1 and SNP in this respect.