Chronic N-G-nitro-L-arginine methyl ester treatment does not prevent flow-induced remodeling in mesenteric feed arteries and arcading arterioles

Although endothelium-derived NO is an important mediator in acute flow-indu ced changes in arterial tone, the role of NO in chronic flow-induced change s in the resistance artery and arteriolar structure remains largely unresol ved. We investigated the effects of chronic inhibition of NO synthase on ar terial and arteriolar remodeling in a rat mesenteric model in which flow ch anges were induced. Alternating first-order mesenteric arteries were ligate d to shunt blood flow through the intermittent patent. arteries. Animals re ceived no treatment (NT) or a continuous infusion of N-G-nitro-L-arginine m ethyl ester (L-NAME, 25 mg/kg SC per day). After 2 weeks, local in vivo blo od flow and in vitro arterial pressure-diameter relationships were assessed , as were the in situ diameters of arcading arterioles. Medial cross-sectio nal areas (CSAs) were measured histologically. In both groups of animals, b lood flow was significantly increased in patent arteries and decreased in l igated arteries compared with control vessels. Nonetheless, in L-NAME-treat ed rats, patent artery flow was increased to a lesser extent, although cont rol flow was not significantly reduced (0.18+/-0.05 versus 0.26+/-0.05 mL/m in). In NT rats, the diameter of patent arteries was significantly larger a nd the diameter of ligated arteries was significantly smaller than that of control arteries. CSAs displayed the same pattern of change (11.9+/-0.6x10( 3), 6.1+/-0.7x10(3), and 8.2+/-1.0x10(3) mu m(2) for patent, ligated, and c ontrol arteries, respectively). Arterioles in the NT collateral pathway (21 8+/-15 mu m) had diameters similar to control arteriole diameters (201+/-15 mu m) but had a significantly larger CSA (6.2+/-0.6x10(3) versus 4.2+/-0.4 x10(3) mu m(2)). In L-NAME-treated rats, the flow-induced changes of the di ameter and CSA in patent arteries, ligated arteries, and arcading arteriole s mimicked those in NT rats. Nonetheless, control feed arteries (430+/-21 v ersus 497+/-16 mu m) and arcading, arterioles (156+/-21 mu m) were signific antly narrower after L-NAME treatment. Thus, chronic blockade of NO oxide s ynthase (1) tended to reduce arterial blood flow and resulted in inward rem odeling of mesenteric arteries and arterioles and (2) did not prevent arter ial and arteriolar remodeling in response to imposed changes in blood flow. Endothelium-derived mediators other than NO can play a major role in flow- induced arterial remodeling.