Angiotensin II AT1 receptor blockade prevents gastric ulcers during cold-restraint stress
Annals of the New York Academy of Sciences
Angiotensin II receptors; AT receptor antagonists 1; Inflammation; Prevention and treatment; Stress ulcers
Cold-restraint stress reduces gastric blood flow and produces acute gastric ulcers. We studied the role of Angiotensin II (Ang II) on gastric blood flow and gastric ulceration during stress. Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated for 14 days with the AT1 receptor antagonist candesartan before cold-restraint stress. AT1 blockade increased gastric blood flow 40% to 50%; prevented gastric ulcer formation by 70% to 80%; reduced the increase in adrenomedullary epinephrine and TH mRNA without preventing the stress-induced increase in adrenal corticosterone; decreased the stress-induced expression of tumor necrosis factor α (TNF-α) and adhesion protein ICAM-1 in arterial endothelium, and neutrophil infiltration in the gastric mucosa; and decreased PGE2 content. AT1 receptor blockers prevent stress-induced ulcerations by a combination of gastric blood flow protection, decreased sympathoadrenal activation, anti-inflammatory effects with reduction in TNF-α, and ICAM-1 expression, leading to reduced neutrophil infiltration while maintaining the protective glucocorticoid effects and PGE2 release. Ang II has a crucial role, through stimulation of AT1 receptors, in the production and progression of stress-induced gastric injury, and AT1 receptor antagonists could be of therapeutic benefit.
Bregonzio, C., Armando, I., Ando, H., Jezova, M., Baiardi, G., & Saavedra, J. (2004). Angiotensin II AT1 receptor blockade prevents gastric ulcers during cold-restraint stress. Annals of the New York Academy of Sciences, 1018 (). http://dx.doi.org/10.1196/annals.1296.044