Flow (shear stress)-mediated dilation (FMD) plays a key role in the local control of vascular diameter and blood flow supply. Although vasodilator treatments improve FMD in diverse models of hypertension, FMD may also change in situations where systemic blood pressure is not affected. In pathological situations such as ischemia, local blood flow and vascular density are increased by vasodilators not affecting systemic blood pressure. As the mechanisms involved remain obscure, we studied FMD in resistance arteries from mice treated chronically (1 month) with hydralazine (200 mg/L in drinking water). Blood flow in mesenteric arteries of mice treated with hydralazine was significantly increased (130 +/- 15 to 169 +/- 27 microl/min, n = 10/group), whereas mean arterial blood pressure was not affected (79 +/- 5 vs 82 +/- 3 mm Hg in controls). Mesenteric resistance arteries (90 microm internal diameter, 75 mm Hg) were isolated and mounted in vitro in an arteriograph. Pressure (myogenic tone)-, phenylephrine-, and KCl-induced contractions, as well as acetylcholine- and sodium nitroprusside-induced dilations, were unaffected by hydralazine. Flow-mediated dilation in arteries from hydralazine-treated mice was significantly increased, especially for low flow values (up to sevenfold). L-NAME-sensitive and indomethacin-sensitive FMD were both increased by hydralazine. Passive arterial diameter increased and arterial wall thickness decreased after chronic hydralazine. This is the first functional evidence that flow (shear stress)-mediated dilation in resistance arteries is improved by a chronic treatment with a nonselective vasodilator. This arteriolar adaptation to a chronic increase in blood flow might be of importance in the pathophysiology of ischemic diseases.