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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

The spontaneously hypertensive rats (SHR) are a genetically hypertensive strain with vulnerability to brain ischemia and stress. In SHR, the brain Angiotensin II (Ang II) system is chronically stimulated, resulting in brain artery remodeling and inflammation. Pretreatment with Ang II AT1 receptor antagonists protects from brain ischemia and prevents the hormonal and sympathoadrenal response to stress. In addition, the anti-inflammatory effects of AT1 receptor antagonists are partially responsible for preventing the development of stress-induced gastric ulcers. We asked whether AT1 receptor antagonists could exert anti-inflammatory effects in the brain vasculature as a mechanism for their protective effects against ischemia. As determined by immunohistochemistry, long-term inhibition of brain AT1 receptors by peripheral administration of the AT1 receptor antagonist candesartan (0.3 mg/kg/day for 28 days) normalized the pathologic remodeling, decreased expression of the intercellular adhesion molecule-1 and the number of associated macrophages, and normalized the endothelial nitric oxide synthase expression in cerebral vessels of SHR. The anti-inflammatory effects of AT1 receptor antagonists may be an important mechanism for protection against ischemia and could participate in the anti-stress properties of this class of compounds. [ABSTRACT FROM AUTHOR]

A 2-week pretreatment with an Angiotensin II AT1 antagonist prevented the adrenomedullary and hormonal response to isolation stress. We studied the effect of life-long treatment with the AT1 receptor antagonist candesartan, 10 mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of age on the response to stress of stress-sensitive spontaneously hypertensive rats (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were submitted to 24-h isolation stress at different times during the treatment. Treatment with candesartan extended the lifespan of SHRs. AT1 receptor blockade retained its capacity to blunt the response to isolation stress over a long period of treatment. The AT1 antagonist inhibited epinephrine release in SHR but not in WKY rats during the first 3 months, corticosterone release in SHR and WKY rats during 10 months, and vasopressin release in SHR rats during 18 months of treatment when rats were submitted to isolation stress. There were no changes in vasopressin release in WKY rats during stress or after AT1 receptor blockade. We conclude that the blockade of the stress response by the AT1 receptor antagonist is long lasting and differs between stressprone SHR and WKY rats and that the specific components of the stress response (sympathoadrenal activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin release) react differently to AT1 receptor blockade. The longterm protective effects of AT1 receptor blockade can be important in animals vulnerable to stress and, in conjunction with the normalization of blood pressure, can prolong lifespan through end-organ protection. [ABSTRACT FROM AUTHOR]

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 coldrestraint 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-α 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-α 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. [ABSTRACT FROM AUTHOR]

Examines the estrogen upregulation of renal angiotensin in mammalian kidney. Production of sodium retention with the stimulation of renal At[sub 2] receptor; Measurement on the total binding activity of compounds; Administration of supraphysiological dose of estradiol in the blood level.