The aim of this study was to evaluate the influence of endogenous nitric oxide on resting microvascular tone in the Dahl salt-sensitive (DS) rat and to determine how this influence is altered in salt-induced hypertension. Intravital microscopy was used to examine the arteriolar network in the spinotrapezius muscle of DS rats maintained on low (0.45% NaCl) or high (4% NaCl) salt diets for 6-7 weeks. Mean arterial pressure for DS rats on high salt (163±3 mm Hg) was significantly greater than that for DS rats on low salt (128±4 mm Hg). Inhibition of microvascular nitric oxide synthesis with A rG -nitro-L-argininemethyl ester caused arteriolar constriction in normotensive DS but not in hypertensive DS rats. Application of L-arginine consistently caused arteriolar dilation in normotensive DS but not hypertensive DS rats. In contrast, arteriolar responses to iontophoretically applied acetylcholine and sodium nitroprusside were similar in both groups. These results indicate that basal release of nitric oxide, presumably from the endothelium, normally influences arteriolar tone in skeletal muscle of DS rats and that this influence is suppressed in established salt-induced hypertension. However, the normal arteriolar response to acetylcholine in hypertensive DS rats suggests that a generalized impairment of endothelial function may not occur in the microcirculation of these animals. Unaltered arteriolar responsiveness to sodium nitroprusside in hypertensive DS rats also suggests that salt-induced hypertension is not accompanied by a change in the responsiveness of arteriolar smooth muscle to nitric oxide. (Hypertension 1992;19:290-295) KEYWORDS • hypertension • microcirculation • endothelium • nitric oxide • endothelium-derived relaxing factor W hen fed a high salt diet, the Dahl salt-sensitive (DS) rat develops hypertension that is chiefly due to increased total peripheral resistance. 12 Accordingly, the vascular tone of large arterioles is increased in skeletal muscle of hypertensive DS rats, reducing the average internal diameter of these vessels after 4 weeks of high salt intake. 3 Since acetylcholine (ACh) was first shown to cause vasodilation through the release of a relaxing factor from the endothelium, 4 other endothelium-derived factors have been identified and their importance in regulating vascular tone has been recognized. 5 -6 The factor released by ACh is thought to be nitric oxide (NO) or a compound that spontaneously generates NO. 5 -7 Chronic hypertension alters endothelial cell morphology and function, 8 -10 and a reduced relaxation response to ACh and other endothelium-dependent agonists has been observed in large arteries from the hypertensive DS rat and other models of hypertension."-15 However, A portion of this work was presented at the Fifth World Congress for Microcirculation, Louisville, Ky., August 31-September 5, 1991.Supported by grant HL-44012 from the National Heart, Lung, and Blood Institute and by a Grant-in-Aid from the American Heart Association, West Virginia Affiliate.Address for...