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1. The effect of vagotomy on gastric acid secretion was studied in chronic gastric fistula rats at various times after denervation. In these rats basal and pentagastrin-induced acid output was permanently reduced. Thus, the magnitude of the acid response to pentagastrin in the conscious fistula rat is dependent upon an intact vagus. 2. The acid response to pylorus ligation in vagally intact rats was unaffected by drainage of the stomach and therefore not caused by distension. Bilateral vagotomy, performed simultaneously with the ligation, completely abolished acid secretion, while unilateral vagotomy reduced the acid output by half. Hence, in innervated rats, an intact vagal impulse flow appears to be essential for the acid response to pylorus ligation. When the pylorus ligation was performed 2-8 weeks after truncal vagotomy, the acid output showed a progressive return towards pre-denervation values. In the denervated rats the acid response to pylorus ligation was blocked by drainage of the stomach and therefore probably caused by distension, a mechanism which is independent of the vagal impulse flow. 3. The response to pylorus ligation in innervated rats was blocked by atropine and chlorisondamine but not by metiamide. In the denervated rats, the response to pylorus ligation was blocked by all three drugs. 4. Following ligation of both the pylorus and the oesophagus the acid response was poor. With drainage of the oesophagus the acid response was much enhanced, suggesting that oesophageal distension inhibits acid secretion. In the vagotomized rat the poor acid response to oesophageal + pyloric ligation could not be overcome by drainage of the oesophagus. In the innervated rat gastric distension could overcome the inhibition induced by oesophageal ligation. Also in chronically, but not in acutely vagotomized rats, gastric distension brought about a good acid response. Conceivably, gastric reflex mechanisms can activate acid secretion through vagal and/or intramural pathways. Both in innervated and denervated rats the response to gastric distension was inhibited by atropine, chlorisondamine and metiamide. 5. The results suggest that in the innervated rat vago-vagal reflexes are important for the gastric hypersecretion following ligation of the pylorus, and for the acid response to gastric distension following ligation of the pylorus and oesophagus. In the chronically vagotomized rat local intramural reflexes elicited by gastric distension are responsible for the acid response.
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