The effect of eprosartan on reflex sympathetic activation in sodium restricted patients with essential hypertension.

AT(1) receptor antagonists possess sympathoinhibitory effects in animal experiments, but in human studies the results are conflicting. We tested the hypothesis that very short-term treatment with the AT(1) receptor antagonist eprosartan inhibits reflex activation of the sympathetic nervous system in sodium-restricted patients with essential hypertension. The effect of eprosartan on urinary sodium and lithium excretion, heart rate, blood pressure, and vasoactive hormones was measured during reflex activation of the sympathetic nervous system by a cold pressor test and by a sodium nitroprusside induced 10 mm Hg reduction of the mean arterial pressure. It was a randomized, placebo-controlled, double-blinded, crossover study in 14 patients with essential hypertension. Glomerular filtration rate and renal tubular function were determined with continuous infusion clearance technique and vasoactive hormones with radioimmunoassays. Eprosartan had no effect on the increases in heart rate and plasma levels of noradrenaline during reflex activation of the sympathetic nervous system. However, eprosartan significantly decreased in fractional excretions of sodium (mean ± SD) (0.23 ± 0.22%) and lithium (3.1 ± 1.7%) during the sodium nitroprusside infusion, compared to placebo. Very short-term eprosartan treatment does not seem to have any sympathoinhibitory effects in sodium restricted patients with essential hypertension.

Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels.

BACKGROUND: Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. METHODS: The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. RESULTS: Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. CONCLUSION: During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system TRIAL REGISTRATION: Clinical Trials Identifier: NCT00281762.