Effect of topical histamine on mucosal microvascular permeability and acid secretion in the rat stomach

The effect of topical histamine on microvascular permeability to macromolecules was studied in the rat gastric mucosa using a fluorescent in vivo microscopy technique. Acid secretion was measured in the pylorus-ligated rat. A topical dose of 10(-2)M histamine increased acid output to a maximum, which was equal to the maximum values attained by intravenous or subcutaneous histamine. Only in rats pretreated with a beta-adrenergic antagonist did 10(-2) to 5 X 10(-2)M histamine cause leak of a fluorescein-albumin conjugate from mucosal microvessels. Leak occurred around collecting venules but not from capillaries. An H1-receptor antagonist, but not an H2-receptor antagonist, significantly decreased histamine-induced leaks. We concluded the following. 1) topically applied histamine penetrates into the mucosa and can increase acid secretion to the same extent as parenteral histamine. 2) Topical histamine increases microvascular permeability to macromolecules only when beta-adrenergic receptors are blocked. Larger doses of histamine are needed for initiating the permeability change than for initiating the acid secretory response. 3) H1-receptors in venules are involved in the histamine-induced increase in permeability.