Omeprazole induces high intraglandular pressure in the rat gastric mucosa

In a few patients receiving high doses of omeprazole for a prolonged period, cystic changes have developed in the gastric mucosa, possibly consisting of enlarged gland lumina. To investigate this question, the luminal pressure in gastric glands was studied after omeprazole treatment in Inactin-anesthetized rats.

The gland luminal pressure and mucus thickness were measured with microelectrodes. For pressure measurements (servo-null technique) the microelectrode was inserted into a gland at an angle of approximately 30 degrees to the mucosal surface.

Animals given omeprazole by gavage, 400 micromol/kg daily for 1 week, showed high gland luminal pressures (27.4 +/- 2.4 mm Hg). Similar values were found in animals given an intravenous omeprazole injection (40 micromol/kg). Much lower pressures were noted after vehicle or pentagastrin infusion. The thickness of the lower, firm mucus layer was not altered by omeprazole treatment.

The significantly higher gland luminal pressure after treatment with omeprazole, compared with the values during pentagastrin or vehicle infusion, cannot be explained by increased mucus thickness. The results suggest accumulation of fluid in the gland lumen caused by increased resistance to outflow from the gland. This might explain the proposed enlargement of gland lumina.