Flow regulates EDRF/NO production in the isolated canine mesenteric arterial bed

It has been demonstrated that the amount of vasoactive substances released from vascular endothelial cells varies in response to changes in blood flow and/or blood pressure. In the present study, we tried to estimate the influence of these hemodynamic factors on the production of EDRF/NO in the resistance arteries by using canine mesenteric arterial bed preparations perfused with Krebs-Henseleit solution. Under inhibition of cyclooxygenase by indomethacin (5 μM), increases in the flow rate (8-40 ml/min) resulted in elevations of perfusion pressure. These responses were potentiated by N^G -nitro-L-arginine (L-NNA, 100 μM), indicating involvement of the NO-cyclic GMP system. The amount of NO released from the endothelium at various flow rates was estimated by the following two experiments：1) comparison of the flow-pressure curves obtained with the perfusate containing various concentrations of sodium nitroprusside in the presence or absence of L-NNA and 2) measurement of output of cyclic GMP from the vascular bed preparation. Results obtained from these experiments indicate that increase in the flow rate augments NO production in the canine mesenteric arterial bed. Thus, flow and/or pressure seems to be an important determinant(s) of the function of endothelial cells lining resistance arteries.