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

Background: Spontaneously hypertensive rats (SHR) are a representative anim al model for disturbance of the pituitary-adrenal axis, as well as disturba nce of the autonomic nervous system. Methods and Results: In this study, we showed that adrenalectomy in SHR-ind uced spontaneous gastric ulcer formation. We further investigated how abnor mal adrenal secretion is related to the attenuation of gastric ulcerogenesi s, in terms of leucocyte infiltration and nitric oxide (NO) formation. Bila teral adrenalectomy, as well as a sham-operation, were carried out at 12 we eks in hypertensive SHR and Wistar-Kyoto rats (WKY) and observations were m ade three weeks later. The number of myeloperoxidase (MPO) positive cells, NADPH diaphorase histochemistry and NO synthase (NOS) activity were determi ned in gastric specimens. Only in adrenalectomized, but not sham-operated S HR, WKY and adrenalectomized WKY, could gastric ulcers be observed. Althoug h the number of cells positive for MPO was significantly lower in hypertens ive SHR than those in WKY, such cells were increased after adrenalectomy in SHR. In contrast, adrenalectomized WKY developed no increase in MPO-positi ve numbers. The number of NADPH diaphorase-positive cells increased after a drenalectomy in both strains, the extent of which was much greater in SHR t han 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 ul ceration may be associated with entrapment of activated leucocytes in the g astric mucosa, as well as with an excessive production of NO in adrenalecto mized SHR. An enhanced adrenal glucocorticoid may be a key factor for prote cting the gastric mucosa in SHR.