Role of endogenous endothelin-1 in stress-induced gastric mucosal damage and acid secretion in rats

• Published in: Regulatory peptides Vol. 73; no. 1; pp. 43 - 50
• Main Authors: Said, Shehta A, El-Mowafy, Abdalla M
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 02.01.1998; Amsterdam Elsevier
• Subjects: Animals; Biological and medical sciences; Bosentan; Endothelin level; Endothelin Receptor Antagonists; Endothelin-1 - analysis; Gastric acid; Gastric Acid - metabolism; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Male; Medical sciences; Other diseases. Semiology; Peptic ulcer; Peptic Ulcer Hemorrhage - etiology; Rats; Rats, Sprague-Dawley; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Stress; Stress, Physiological - physiopathology; Sulfonamides - pharmacology; Water immersion; Endothelin level; Peptic ulcer; Bosentan; Gastric acid; Water immersion; Stress; Stomach; Rat; Digestive system; Pathogenesis; Rodentia; Endothelin 1; Vertebrata; Mammalia; Peptidergic receptor; Digestive diseases; Antagonist; Exocrine secretion; Anastomotic ulcer; Gastric disease
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/S0167-0115(97)01056-2

In rats subjected to 8 h water-immersion stress, gastric and duodenal mucosal hemorrhage and erosions were detected by macroscopic and histopathological examination. Moreover, plasma and gastric mucosal endothelin-1 (ET-1) levels rose appreciably in a time-related manner during water immersion, with a higher concentration detected in gastric mucosa. Thus, the percentage increases in plasma (gastric mucosal) ET-1, relative to basal levels, after 1, 4 and 8 h of water immersion were 86(172), 169(322) and 210(391)%, respectively. Likewise, a marked increase of gastric acid output was demonstrated 30 min after water immersion and lasted for 3 h. Pretreatment with the endothelin ET A/ET B receptor blocker, bosentan (30 and 100 mg kg −1), orally, dose-dependently antagonized gastric and duodenal mucosal damage as indicated by reductions in lesion lengths of 67 and 80%, respectively. Similar protective effects on mucosa were observed when bosentan was given by the intramuscular route. On the other hand, bosentan suppressed the rate of acid output by 30.3±2.1% in the stressed rats, but had no such effect in non-stressed animals. Taken together, results from this study implicate the endogenous peptide, ET-1, as a powerful mediator of stress-evoked gastro-duodenal mucosal damage and, moreover, present bosentan as a potential protector against hyperacidity and mucosal erosion that occur as a consequence of stress.