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The driving force for creation of channels in gastric mucus, for acid and pepsin transport, ismost probably the hydrostatic pressure generated within the gastric gland lumen. The aim ofthis study was to investigate the origin and regulation of the glandular pressure. In addition,several parameters known to play an important role in mucosal protection were investigated inrelation to glandular pressure. The study was performed in vivo in exposed gastric mucosa ofInactin^@-anesthetized rats. Glandular pressure, epithelial cell surface pH and mucus gelthickness were measured with microelectrodes, mucosal blood flow by laser Dopplerflowmetry, and mucosal permeability by clearance of ⁵¹Cr-EDTA from blood to lumen.Specimens of mucosa were also investigated immunohistochemically.

Actin immunostaining revealed muscle strands arising from muscularis mucosa and branchingat the gastric pits. Vasoactive intestinal peptide (VIP)- containing nerve fibers were found inclose relation to these muscle strands. Administration of VIP decreased glandular pressure,probably by relaxing the muscle strands.

The glandular pressure decreased along with the reduction in acid/volume secretion whensecretagogue infusion was terminated or when acid secretion was blocked by ranitidine.Omeprazole administration, in contrast, sustained or increased the pressure despite totalinhibition of acid secretion, probably by increasing resistance to outflow of the glands,resulting in intraglandular volume accumulation and dilatation of the glands.

Prostaglandin E₂ greatly increased glandular pressure in low doses that did not affect bloodflow, acid secretion or mucus thickness, while indomethacin decreased the pressure.Aggressive factors (ethanol and HCl) applied topically increased the pressure, probably byreleasing prostaglandins, since indomethacin pretreatment inhibited this response.

Topical administration of acid (pH 1) increased permeability and blood flow in the nonacid-secreting mucosa and decreased epithelial cell surface pH. High endogenous acid secretion ori.v. infusion of bicarbonate protected the mucosa.

Conclusions: The histologically observed mucosal muscles provide a morphological basis forcreation of an intraglandular pressure. Despite total inhibition of acid secretion some glandularpressure always remains. Endogenous prostaglandins are probably important for maintenanceof a high glandular pressure. The acid-secreting mucosa has a better buffering capacity byvirtue of increased bicarbonate delivery from the parietal cells through the surface epithelium tothe mucus.