Protective role of adrenal glucocorticoids for gastric mucosa in spontaneously hypertensive rats

Background: Spontaneously hypertensive rats (SHR) are a representative animal model for disturbance of the pituitary-adrenal axis, as well as disturbance of the autonomic nervous system. Methods and Results: In this study, we showed that adrenalectomy in SHR-induced spontaneous gastric ulcer formation. We further investigated how abnormal adrenal secretion is related to the attenuation of gastric ulcerogenesis, in terms of leucocyte infiltration and nitric oxide (NO) formation. Bilateral adrenalectomy, as well as a sham-operation, were carried out at 12 weeks in hypertensive SHR and Wistar-Kyoto rats (WKY) and observations were made three weeks later. The number of myeloperoxidase (MPO) positive cells, NADPH diaphorase histochemistry and NO synthase (NOS) activity were determined in gastric specimens. Only in adrenalectomized, but not sham-operated SHR, WKY and adrenalectomized WKY, could gastric ulcers be observed. Although the number of cells positive for MPO was significantly lower in hypertensive SHR than those in WKY, such cells were increased after adrenalectomy in SHR. In contrast, adrenalectomized WKY developed no increase in MPO-positive numbers. The number of NADPH diaphorase-positive cells increased after adrenalectomy in both strains, the extent of which was much greater in SHR than in WKY. Although NOS activity in SHR was lower than that in WKY, it was significantly increased after adrenalectomy. Conclusions: Our data show that the development of a significant gastric ulceration may be associated with entrapment of activated leucocytes in the gastric mucosa, as well as with an excessive production of NO in adrenalectomized SHR. An enhanced adrenal glucocorticoid may be a key factor for protecting the gastric mucosa in SHR.