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 inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). We assessed hydraulic conductivity (L(p)) 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 reduced L(p) by nearly 50% (from a median of 2.4 x 10(-7) cm x s(-1) x cmH(2)O(-1), n = 17, P < 0.001). The reduction in L(p) by L-NAME was inhibited by a 10-fold molar excess of L-arginine but not D-arginine (n = 6). In a separate group of venules, blood flow was allowed to resume during exposure to L-NAME. In vessels perfused by blood during L-NAME exposure, L(p) increased by 78% (from 1.4 x 10(-7) cm x s(-1) x cmH(2)O(-1), n = 10, P < 0.01). N(G)-nitro-D-arginine methyl ester did not affect L(p) 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.
Rumbaut
R E
RE
Pulmonary and Critical Care Division, Department of Internal Medicine, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
Wang
J
J
Huxley
V H
VH
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014699:Venules / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester