Differential effects of l-NAME on rat venular hydraulic conductivity


The role of nitric oxide (NO) in microvascular permeability remains unclear because both increases and decreases in permeability by NO synthase (NOS) inhibitors have been reported. We sought to determine whether blood-borne constituents modify venular permeability responses to the NOS inhibitorNG-nitro-l-arginine methyl ester (l-NAME). We assessed hydraulic conductivity (Lp) of pipette-perfused rat mesenteric venules before and after exposure to 10-4 M l-NAME. In the absence of blood-borne constituents, l-NAME reducedLp by nearly 50% (from a median of 2.4 × 10-7cm · s-1 · cmH2O-1,n = 17, P < 0.001). The reduction inLp by l-NAME was inhibited by a 10-fold molar excess of l-arginine but notd-arginine (n = 6). In a separate group of venules, blood flow was allowed to resume during exposure tol-NAME. In vessels perfused by blood duringl-NAME exposure, Lp increased by 78% (from 1.4 × 10-7cm · s-1 · cmH2O-1,n = 10, P < 0.01).NG-nitro-d-arginine methyl ester did not affect Lp in either of the two groups. These data imply that NO has direct vascular effects on permeability that are opposed by secondary changes in permeability mediated by blood-borne constituents.


Biomedical Sciences

Document Type





microvascular permeability, arginine, endothelium, rat, nitric oxide synthase

Publication Date


Journal Title

American Journal of Physiology-Heart and Circulatory Physiology