Hypertension caused by deoxycorticosterone-salt (DOC-salt) may involve enhanced sympathetic tone and some diuretics may exert their antihypertensive action by modulating presynaptic adrenergic sensitivity. This study analyzes the noradrenergic sensitivity of the perfused mesentery isolated from DOC-salt hypertensive rats treated or not with chlorthalidone. Chlorthalidone treatment reduced arterial hypertension in DOC-salt treated rats (from 160 +/- 7 to 127 +/- 5 mmHg). The diuretic completely prevented the increase in sympathetic tone and blunted the decreased vagal tone observed in DOC-salt rats. Norepinephrine-induced vasoconstriction was enhanced in perfused mesenteries isolated from DOC-salt rats. This alteration was attenuated in preparations from chlorthalidone-treated DOC-salt animals. Blockade of neuronal catecholamine uptake using cocaine did not change these responses. These data suggest that chlorthalidone reduces the vascular hyperresponsiveness to catecholamines observed in DOC-salt treated hypertensive rats.