The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8 +/- 3.6%, decreased papillary blood flow by 39.4 +/- 3.8%, and decreased renal blood flow by 47.4 +/- 1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2 +/- 2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n = 6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6 +/- 2.1% without significantly altering mean arterial ressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9 +/- 1.8%) and renal blood flow (49.8 +/- 6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure-renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure-papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure-papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure-blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.