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-induced changes in arterial tone, the role of NO in chronic flow-induced changes in the resistance artery and arteriolar structure remains largely unresolved. We investigated the effects of chronic inhibition of NO synthase on arterial and arteriolar remodeling in a rat mesenteric model in which flow changes were induced. Alternating first-order mesenteric arteries were ligated to shunt blood flow through the intermittent patent arteries. Animals received no treatment (NT) or a continuous infusion of N:(G)-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg SC per day). After 2 weeks, local in vivo blood flow and in vitro arterial pressure-diameter relationships were assessed, as were the in situ diameters of arcading arterioles. Medial cross-sectional areas (CSAs) were measured histologically. In both groups of animals, blood flow was significantly increased in patent arteries and decreased in ligated arteries compared with control vessels. Nonetheless, in L-NAME-treated rats, patent artery flow was increased to a lesser extent, although control flow was not significantly reduced (0.18+/-0.05 versus 0.26+/-0.05 mL/min). In NT rats, the diameter of patent arteries was significantly larger and the diameter of ligated arteries was significantly smaller than that of control arteries. CSAs displayed the same pattern of change (11. 9+/-0.6 x 10(3), 6.1+/-0.7 x 10(3), and 8.2+/-1.0 x 10(3) microm(2) for patent, ligated, and control arteries, respectively). Arterioles in the NT collateral pathway (218+/-15 microm) had diameters similar to control arteriole diameters (201+/-15 microm) but had a significantly larger CSA (6.2+/-0.6 x 10(3) versus 4.2+/-0.4 x 10(3) microm(2)). In L-NAME-treated rats, the flow-induced changes of the diameter and CSA in patent arteries, ligated arteries, and arcading arterioles mimicked those in NT rats. Nonetheless, control feed arteries (430+/-21 versus 497+/-16 microm) and arcading arterioles (156+/-21 microm) were significantly narrower after L-NAME treatment. Thus, chronic blockade of NO oxide synthase (1) tended to reduce arterial blood flow and resulted in inward remodeling of mesenteric arteries and arterioles and (2) did not prevent arterial 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.