Effects of flow rate changes on nitric oxide (NO) formation in vascular endothelial cells were investigated in isolated canine mesenteric arterial bed preparations. Stepwise increases in the flow rate from 8 ml/min to 40 ml/min significantly (P <0.05) elevated perfusion pressure in a rate-dependent manner. In the presence of N(G)-nitro-L-arginine (L-NNA, 100 microM), perfusion pressures were significantly (P<0.01) higher than those observed under control conditions at all flow rates examined. Sodium nitroprusside (SNP) (0.1-10 microM) counteracted the pressor effect of L-NNA in a concentration-dependent manner. Increases in the flow rate from 10 ml/min to 40 ml/min significantly (P < 0.05) augmented cyclic GMP production in the vascular bed preparation. The flow-induced cyclic GMP response was significantly (P <0.05) attenuated by L-NNA (100 microM). These results demonstrate that 1) the amount of NO released from endothelial cells toward vascular smooth muscle cells can be semi-quantified with SNP, and 2) an increase in the flow rate stimulates NO formation in endothelial cells of resistance arteries, which may play an important part in regulating systemic blood pressure.