Asynchrony in circadian rhythms of gastric function in the rat. A model for gastric mucosal injury.
A model for gastric mucosal injury is proposed in which a key pathogenetic event is the disruption in the normal relationships among several circadian rhythms of gastric function. In the rat a circadian rhythm in acid secretion was found to be out of phase with a circadian rhythm in gastric pepsin secretion, another aggressive factor, and several mucosal defensive factors (mucus and bicarbonate efflux and tissue prostacyclin content). Gastric corpus mucosal blood flow circadian patterns paralleled the the rhythmicity in acid secretion and, therefore, was out of phase with the other measured mucosal defensive factors. Thus, gastric mucosal defense was maintained by different mechanisms over the 24-hr cycle. During the dark phase, when this species was active and when acid secretion was highest, enhanced damage by topical acidified aspirin was documented, despite increased mucosal blood flow. Natural asynchrony in circadian rhythms of gastric function can be protective of gastric mucosal integrity but disruption of this circadian interplay of gastric aggressive and defensive factors could theoretically lead to greater vulnerability to damage. In the human, a circadian rhythm in basal gastric acidity has been described but no information exists as to the possibility of similar rhythmic variation in other gastric factors (aggressive and defensive) and possible disruption of these rhythms in disease.
Moore
J G
JG
Department of Medicine, Salt Lake Veterans Affairs Medical Center, Utah 84148.
Larsen
K R
KR
Barattini
P
P
Dayton
M T
MT
D000818:Animals; D001241:Aspirin; D001639:Bicarbonates / Q000032:analysis; D002927:Cimetidine / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000032:analysis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010434:Pepsin A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology*
D001639:Bicarbonates; D002927:Cimetidine; D011464:Epoprostenol; D010434:Pepsin A; D001241:Aspirin