Effect of histamine and histamine antagonists on human lower esophageal sphincter function

The purpose of this study was to evaluate the effect of histamine phosphate and specific histamine antagonists on human lower esophageal sphincter (LES) pressure. Continuous intravenous infusions of histamine at doses of 2.0 to 40.0 microgram/kg-hr gave graded increases in LES pressure with a peak response of 378 +/- 4.6 mm Hg at 20.0 microgram kr-hr. The LES response was not altered by an H1-antogonist, diphenhydramine (50 mg, intravenously), but was completely blocked by infusion of the H2-antagonist, cimetidine (4.0 mg/kg-hr). Also, oral cimetidine (300 mg) antagonized any increase in LES pressure during histamine infusion at a dose shown to give the maximal LES response. Despite this effect of cimetidine in antagonizing the maximal LES response to histamine, oral cimetidine at 200, 300, and 400 mg failed to alter basal LES pressure over a 3-hr period. Cimetidine also failed to alter the LES response to intravenous pentagastrin or oral beef hydrolysate. These studies suggest that: (1) human LES pressure increases in response to intravenous histamine phosphate through its action at an H2-receptor; (2) the H1-receptor has no apparent role in the human LES response to histamine; and (3) H2-antagonism with cimetidine has no effect on the human LES basal pressure or its response to gastrin stimulation.