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Stress reduces gastric blood flow and produces acute gastric mucosal lesions. We studied the role of angiotensin II in gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats were pretreated for 14 days with the [AT.sub.1] receptor antagonist candesartan before cold-restraint stress. [AT.sub.1] receptors were localized in the endothelium of arteries in the gastric mucosa and in all gastric layers. [AT.sub.1] blockade increased gastric blood flow by 40-50%, prevented gastric ulcer formation by 70-80% after cold-restraint stress, reduced the increase in adrenomedullary epinephrine and tyrosine hydroxylase mRNA without preventing the stress-induced increase in adrenal corticosterone, decreased the stress-induced expression of TNF-[alpha] and that of the adhesion protein ICAM-1 in arterial endothelium, decreased the neutrophil infiltration in the gastric mucosa, and decreased the gastric content of [PGE.sub.2]. [AT.sub.1] receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, and anti-inflammatory effects (with reduction in TNF-[alpha] and ICAM-1 expression leading to reduced neutrophil infiltration) while maintaining the protective glucocorticoid effects and [PGE.sub.2] release. Angiotensin II has a crucial role, through stimulation of [AT.sub.1] receptors, in the production and progression of stress-induced gastric injury, and [AT.sub.1] receptor antagonists could be of therapeutic benefit. gastric blood flow; prostaglandins; tumor necrosis factor

A[T.sub.2] receptors may act in opposition to and in balance with A[T.sub.1] receptors, their stimulation having beneficial effects. We found renal A[T.sub.2] receptor expression in female mice higher than in male mice. We asked the question of whether such expression might be estrogen dependent. In male, female, ovariectomized, and estrogentreated ovariectomized mice, we studied renal A[T.sub.1] and A[T.sub.2] receptors by immunocytochemistry and autoradiography, A[T.sub.2] receptor mRNA by RT-PCR, and cAMP, cGMP, and PG[E.sub.2] by RIA. A[T.sub.1] receptors predominated. A[T.sub.2] receptors were present in glomeruli, medullary rays, and inner medulla, and in female kidney capsule. A[T.sub.1] and A[T.sub.2] receptors colocalized in glomeruli. Female mice expressed fewer glomerular A[T.sub.1] receptors. Ovariectomy decreased A[T.sub.1] receptors in medullary rays and capsular A[T.sub.2] receptors. Estrogen administration normalized A[T.sub.1] receptors in medullary rays and increased A[T.sub.2] receptors predominantly in capsule and inner medulla, and also in glomeruli, medullary rays, and inner stripe of outer medulla. In medullas of estrogen-treated ovariectomized mice there was higher A[T.sub.2] receptor mRNA, decreased cGMP, and increased PG[E.sub.2] content. We propose that the protective effects of estrogen may be partially mediated through enhancement of A[T.sub.2] receptor stimulation. renin-angiotensin system; reproductive hormones; kidney function; cyclic nucleotides; prostaglandins