Prediction of the lower esophageal sphincter pressure after oral molsidomine by sydnonimine plasma concentrations

BACKGROUND/AIMS: Recent studies suggest that endogenous nitric oxide decreases lower esophageal sphincter pressure (LESP). Substances leading to the formation of nitric oxide, such as molsidomine, decreases the human LESP. It is not yet clear whether this reduction is related to plasma concentrations of molsidomine, the nitrate-active substance sydnonimine (SIN-1) or to serum concentrations of nitrate/nitrite (NOx) as a stable end-product of volatile nitric oxide. METHODOLOGY: We performed a double blind controlled crossover trial in 8 healthy male volunteers. Plasma concentrations of molsidomine, SIN-1 and serum concentrations of NOx as well as esophageal manometry were determined. RESULTS: Mean basal LESP was significantly decreased from 25.4+/-2.8 mmHg to 21.9+/-2.7 mmHg and 21.4+/-2.6 mmHg 2 and 3 hours after molsidomine administration, respectively (mean +/-SEM; n=8; p<0.05). The maximum decrease of LESP from the baseline within 1-4 hours after molsidomine administration was 7.6+/-1.5 mmHg (mean +/-SEM; n=8; p<0.01). The decrease of the LESP correlated significantly with plasma concentrations of SIN-1 (r=-0.53; p=0.002). NOx levels remained unchanged. CONCLUSIONS: Molsidomine decreases the LESP and plasma concentrations of the active metabolite SIN-1 may predict the potency of molsidomine to lower LESP. NOx was useless as a control metabolite to measure the LESP in response to molsidomine in healthy volunteers.