ANG-II PROLONGS SPLANCHNIC NERVE-MEDIATED INHIBITION OF DUODENAL MUCOSAL ALKALINE SECRETION IN THE RAT

Hypovolemia inhibits duodenal mucosal alkaline (HCO3-) secretion by ac tivation of sympathoadrenergic nerves. A possible involvement of the r enin-angiotensin system was investigated. Experiments were performed o n chloralose-anesthetized rats. The mucosal alkaline output by a duode nal segment was measured using in situ pH-stat titration equipment. A modest hypovolemia was induced by bleeding the animals similar to 10% of the total blood volume. This procedure decreased duodenal mucosal a lkaline secretion to a sustained level of similar to 50% of baseline a nd reduced mean arterial pressure by similar to 20 mmHg. Intravenous p retreatment with the angiotensin-converting enzyme (ACE) inhibitor ena laprilate (0.7 mg/kg) or the angiotensin II-receptor antagonist losart an (10 mg/kg) altered the response to hypovolemia to a transient one, and alkaline secretion returned to the control level within 40-50 min. When exogenous angiotensin II was administered intravenously (0.25 an d 0.75 mu g . kg(-1) . h(-1)), a hypovolemia-induced sustained depress ion of the secretion was observed even during ACE inhibition. Direct e lectrical stimulation (3 Hz, 5 V, 5 ms, bilaterally) of the peripheral splanchnic nerves decreased duodenal mucosal alkaline secretion to si milar to 60% of the control level and increased mean arterial pressure by similar to 20 mmHg. However, in enalaprilate-pretreated animals, t he inhibition of alkaline secretion due to splanchnic nerve stimulatio n was transient, a response that became sustained on angiotensin II su bstitution. These results suggest that the renin-angiotensin system pr olongs the sympathoadrenergic inhibition of duodenal mucosal alkaline secretion and that angiotensin II, in this regard, acts mainly on the peripheral sympathetic efferents.