Age-Dependent Role of Vasopressin in Susceptibility of Gastric Mucosa to Indomethacin-Induced Injury

The high prevalence of gastric ulceration underlines the importance of understanding the mechanisms. Based upon its multifactorial role vasopressin (AVP) supposed to be one of the contributory factors however the data are contradictory. The spontaneous AVP-deficient Brattleboro rat seems to be a good tool for studying the role of AVP in physiological processes. However, using adult Brattleboro rats we were unable to confirm any significant effect of AVP deficiency on cold immobilization- and indomethacin-induced ulceration. Although the gastroprotective role of glucocorticoids was confirmed in this strain both with acute dexamethasone pretreatment and adrenalectomy, but AVP deficiency had no influence on indomethacin-induced ulceration in adult rats. While AVP has an age-dependent role in stress hormone regulation and gastric mucosal vulnerability also shows age-dependent alterations, we compared young (4-week-old) rats to old ones (1-year-old). In young rats, the lack of AVP lead to attenuation of indomethacin-induced ulceration, while in old ones in its aggravation. Surprisingly, after refeeding at 4 h we saw the opposite picture: in old rats the AVP deficiency accelerated the healing of indomethacin-induced ulceration, and was protective against intestinal lesions. As AVP is involved in a wide range of physiological processes it may influence a complex process such as ulceration at several central or peripheral points. As the main mechanisms, age-dependent regulation of stress hormone levels and microcirculation could be supposed. Blood glucose levels, prostaglandin E 2 and mucus production as well as regenerative effects may also contribute to the AVP effects. Influence on the circadian clock and mood could also play a role. Taken together, AVP might have dual action on the gastrointestinal tract. A different role could be supposed in young and old populations. On the other hand, AVP may participate differentially in the mechanisms of ulcer formation and healing as well as in the development of gastric and intestinal lesions.