Moxonidine is an imidazoline I1-receptor agonist that centrally acts by reducing the sympathetic tone. Furthermore, proximal tubular I1-receptors have been isolated in human kidneys, but their natriuretic effects have never been demonstrated. Because stress tests elicited a sympathetically mediated increase in blood pressure and in sodium reabsorption, the aim of this study was to assess the effects of moxonidine (0.4 mg/day; 1 month) on stress-induced cardiovascular response and renal sodium handling in hypertensives, in a double-blind, crossover, placebo-controlled study. The stress test used is an efficient and reproducible computerized version of Stroop's stress test. During the experimental sessions, both rest and stress renal functional parameters were determined: glomerular filtration rate (inulin clearance), renal plasma flow (para-aminohippurate clearance), filtration fraction, sodium excretion, and segmental sodium tubular reabsorption (lithium clearance). During the placebo phase, stress induced a significant increase in systolic blood pressure (deltaSBP; 15.8+/-10.7 mm Hg) and diastolic blood pressure (deltaDBP; 8.2+/-6.1 mm Hg). During stress, glomerular filtration rate tended to decrease, whereas renal plasma flow significantly decreased, resulting in a significant increase in filtration fraction. Despite the increase in BP, stress induced a decrease in sodium excretion that was mainly due to a nonsignificant increase in sodium reabsorption in the proximal parts of the tubules. Moxonidine significantly reduced rest and stress BP, but the stress cardiovascular reactivity was not altered. At rest, renal function was well preserved by the treatment. Stress-induced modifications in renal function and sodium handling were not altered by the treatment. In conclusion, moxonidine reduced rest and stress-induced peak BP and preserved basal renal function. The study failed to demonstrate any effect of moxonidine either on basal renal sodium handling or on stress-induced increase in sodium reabsorption.