Effects of rilmenidine on stress-induced peak blood pressure and renal function.

Rilmenidine is an imidazoline I1-receptor agonist that centrally acts by reducing the sympathetic tone. There is strong experimental evidence that natriuresis could be evoked by proximal tubular I1-receptors that have also been isolated in human kidneys. However, in humans, the natriuretic effects of proximal tubular I1-receptors have never been demonstrated. Because stress tests elicited a sympathetically mediated increase in blood pressure and in sodium reabsorption, this study examined whether a short-term infusion of rilmenidine (1 mg) may interfere with stress-induced cardiovascular response and renal sodium handling in normotensive men, in a double-blind, crossover, placebo-controlled study. The stress test used is an efficient and reproducible computerized version of the Stroop's stress test. During the experimental sessions, both basal and stress renal functional parameters were determined: glomerular filtration rate, renal plasma flow, filtration fraction, sodium excretion, and segmental sodium tubular reabsorption (lithium clearance). During the placebo phase, stress induced a significant increase in systolic blood pressure (SBP; 22.2+/-10.1 mm Hg) and diastolic blood pressure (DBP; 11.0+/-5.0 mm Hg). During stress, glomerular filtration rate and renal plasma flow tended to decrease, resulting in a nonsignificant increase in filtration fraction. Despite the increase in BP, stress induced a significant decrease in sodium excretion that was due mainly to a nonsignificant increase in sodium reabsorption in the proximal parts of the tubules. Rilmenidine significantly reduced rest and stress BP, but the cardiovascular reactivity to stress was not altered. The treatment slightly decreased basal glomerular filtration rate and increased renal plasma flow, so that the filtration fraction significantly decreased. The treatment-related decrease in BP was associated with a significant increase in basal sodium reabsorption. Stress-induced modifications in renal function and sodium handling were not altered by the treatment. In conclusion, rilmenidine reduced rest BP and preserved stress-induced reactivity in BP and heart rate. Renal effects of rilmenidine are characterized by a decrease in glomerular filtration rate and in filtration fraction and an increase in sodium reabsorption. The study failed to demonstrate any effect of rilmenidine on stress-induced increase in sodium reabsorption.