In small saline-perfused rabbit mesenteric arteries (diam 221 +/- 4 microns, means +/- SE; n = 48) in situ, the interactions of endothelium-derived relaxing factor (EDRF)-mediated flow-dependent dilation and myogenic constriction were studied. When pump flow was increased two- to fivefold (2.8 +/- 0.1-fold), input perfusion pressure rose by 133 +/- 17%. Vessel diameter first increased passively by 9 +/- 1% and then decreased to or below control values reflecting the vascular myogenic activity. This was followed by a 16 +/- 3% increase in diameter, which was flow dependent, because nonperfused vessels exposed to the same intravascular pressures did not dilate. When the perfusate viscosity was increased with dextran solutions, both the basal diameters and the flow-induced dilator responses were significantly augmented, indicating that the increase in shear stress was the stimulus. The flow-dependent dilation was abolished by inhibition of EDRF with either hemoglobin (10 microM) or NG-nitro-L-arginine (0.3 mM) and also after preincubation with neuraminidase (0.2 U/ml, 30 min), which removes part of the membrane glycocalyx. Thus, myogenic responses in small mesenteric arteries can be effectively opposed by shear-induced release of EDRF. This might be a major mechanism for maintaining adequate tissue perfusion when pressure and shear stress increase simultaneously (e.g., exercise hyperemia, autoregulation) and otherwise myogenic activity would reduce vascular conductivity.
Apamin-sensitive K+ channels mediate an endothelium-dependent hyperpolarization in rabbit mesenteric arteries.