Doses Of Secretin Research Articles

Management of Chronic Pancreatitis

Advances in our understanding of chronic pancreatitis have improved our care of patients with this disease. Although our therapies are imperfect and many patients remain symptomatic, appropriate medical care improves the quality of life in these patients. Proper management requires an accurate diagnosis, recognition of the modifiable causes of disease, assessment of symptoms and complications, treatment of these symptoms and complications utilizing a multidisciplinary team, and ongoing monitoring for the effect of therapy and the occurrence of complications.

Structure and Function of the Pancreas in the Polycystic Kidney Rat

Mutation in the Pkhd1 gene that encodes a ciliary protein, fibrocystin, causes multiple cysts in the kidneys and liver in the polycystic kidney (PCK) rat, a model for human autosomal recessive PCK disease. To clarify the role of primary cilia in the pancreatic duct, we examined the structure and function of the exocrine pancreas of PCK rats. Pancreatic juice and bile were collected from anesthetized rats. Pancreatic ductal structure was analyzed by microdissection and immunohist0chemistry. Histologically pancreatic acini were apparently normal, and no cysts were detected in the pancreas. Larger pancreatic ducts were irregularly dilated with enhanced expression of AQP1 in epithelial cells. The pancreatic duct of PCK rats exhibited significantly (P < 0.05) higher distensibility than that of wild-type (WT) rat at a physiological luminal pressure (3 cm H2O). Pancreatic fluid secretion stimulated with a physiological dose of secretin (0.03 nmol/kg per hour) in PCK rats was significantly smaller than that in WT, but the differences were not significant at higher doses. The amylase responses to carbamylcholine were not different between PCK and WT rats. These findings suggest that fibrocystin/primary cilia-dependent mechanisms may play a role in the regulation of pancreatic ductal structure and fluid secretion.

Diagnostic Efficacy of the Secretin Stimulation Test for the Zollinger-Ellison Syndrome: An Intra-Individual Comparison Using Different Dosages in Patients and Controls

Background/Aims: The secretin stimulation test is the principal diagnostic tool to identify Zollinger-Ellison syndrome (ZES). We investigated, by intra-individual comparison, which dose of secretin results in the highest diagnostic efficacy to identify the ZES. Methods: Fifty-seven paired secretin stimulation tests, using both 0.26 μg/kg and 0.78 μg/kg secretin, performed in 13 ZES patients and 12 controls, were analyzed and the findings confirmed in a validation cohort. Results: A gastrin increase of >100 ng/l was found to be the most sensitive and specific criterion for a positive test. Higher gastrin increases after 0.78 μg/kg compared to 0.26 μg/kg secretin contributed to a slightly more sensitive (82.9 vs. 80.5%) but less specific (68.8 vs. 81.3%) test. A validation cohort, with 98 tests using 0.26 μg/kg secretin in 21 ZES patients and 39 controls, provided similar results. In ZES patients with normal fasting serum gastrin levels (<100 ng/l), there was no diagnostic benefit from the use of a higher secretin dose. Conclusions: The 0.26 μg/kg secretin stimulation test has the best diagnostic efficacy for the ZES.

The Effect of Prior Sphincterotomy on the Secretin-Stimulated Magnetic Resonance Cholangiopancreatography (s-MRCP)

A lack of pancreatic duct compliance and decreased duodenal filling on secretin-stimulated magnetic resonance cholangiopancreatography (s-MRCP) has been noted in patients with chronic pancreatitis. Whether endoscopic sphincterotomy can affect pancreatic duct compliance and duodenal filling on diagnostic s-MRCP is unknown. A retrospective review of patients referred to the authors' clinic from December 2006 to December 2007 was performed. Those patients with no evidence of chronic pancreatitis who underwent s-MRCP were studied. Findings on s-MRCP were analyzed, specifically noting change in pancreatic duct diameter size from baseline to maximum dilation and duodenal filling after secretin administration (0.2 microg/kg intravenous dose of human secretin). Of the 34 patients studied, 12 underwent endoscopic sphincterotomy, and 22 had intact sphincters of Oddi. In the sphincterotomy group, there was a mean change of 0.2 cm (range, 0.0-0.4 cm), while in the nonsphincterotomy group, the mean change was 0.9 cm (range, 0.3-2.0 cm) after secretin administration. The difference was significant (P < .005). Endoscopic sphincterotomy significantly decreases pancreatic duct dilation in response to secretin on s-MRCP. However, further studies are required to determine the effect sphincterotomy has on the amount of duodenal filling and the rate at which duodenal filling occurs.

Secretin‐induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways

Secretin has been shown to delay gastric emptying and inhibit gastric motility. We have demonstrated that secretin acts on the afferent vagal pathway to induce gastric relaxation in the rat. However, the efferent pathway that mediates the action of secretin on gastric motility remains unknown. We recorded the response of intragastric pressure to graded doses of secretin administered intravenously to anaesthetized rats using a balloon attached to a catheter and placed in the body of the stomach. Secretin evoked a dose-dependent decrease in intragastric pressure. The threshold dose of secretin was 1.4 pmol kg(-1) h(-1) and the effective dose, 50% was 5.6 pmol kg(-1) h(-1). Pretreatment with hexamethonium markedly reduced gastric relaxation induced by secretin (5.6 pmol kg(-1) h(-1)). Bilateral vagotomy also significantly reduced gastric motor responses to secretin. Administration of N(G)-nitro-L-arginine methyl ester (10 mg kg(-1)) did not affect gastric relaxation induced by secretin. In contrast, intravenous administration of a vasoactive intestinal polypeptide (VIP) antagonist (30 nmol kg(-1)) reduced the gastric relaxation response to secretin (5.6 pmol kg(-1) h(-1)) by 89 +/- 5%. Indomethacin (2 mg kg(-1)) reduced gastric relaxation induced by secretin (5.6 pmol kg(-1) h(-1)) by 87 +/- 5%. Administration of prostaglandin (48 mg kg(-1) h(-1)) prevented this inhibitory effect. Indomethacin also reduced gastric relaxation induced by VIP (300 pmol kg(-1)) by 90 +/- 7%. These observations indicate that secretin acts through stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. Through nicotinic synapses, secretin stimulates VIP release from postganglionic neurons in the gastric myenteric plexus, which in turn induces gastric relaxation through a prostaglandin-dependent pathway.

Prior Endoscopic Sphincterotomy Can Affect the Interpretation of Secretin-Stimulated Magnetic Resonance Cholangiopancreatography (S-MRCP)

Purpose: Lack of pancreatic duct compliance and decreased duodenal filling on secretin-stimulated magnetic resonance cholangiopancreatography (S-MRCP) has been noted in patients with chronic pancreatitis. As to whether or not endoscopic sphincterotomy (ES) can affect pancreatic duct compliance and duodenal filling on diagnostic S-MRCP is unknown. The purpose of this study was to determine if pancreatic duct compliance and duodenal filling on S-MRCP in patients without evidence of chronic pancreatitis was different in those with and without ES. Methods: A retrospective review of patients who were referred to our pancreatico-biliary clinic from 12/06–12/07 was performed. Those patients who had no evidence of chronic pancreatitis (normal fecal elastase 1 levels and normal MRI or CT imaging and/or normal endoscopic pancreatic function tests) and who underwent S-MRCP were studied. S-MRCP findings were analyzed, specifically noting change in pancreatic duct diameter size from baseline to max dilation after secretin administration (0.2 mcg/kg IV dose of human secretin), the time to achieve max dilation, and the grade of duodenal filling at peak diameter. A single observer measured and recorded all measurements, and the mean for pancreatic duct diameter change, time to peak change, and duodenal filling were calculated. Results: Of the 34 patients studied, 12 had ES and 22 had intact sphincters of Oddi. In the sphincterotomy group, there was a mean change of 0.17 mm (range 0.01–0.35), while in the non-sphincterotomy group, the mean change was 0.91 mm (range 0.31–1.97) after secretin administration. The difference was significant with a P < 0.005. Though there was a trend towards a longer time to maximal pancreatic duct dilation and lower duodenal filling at peak pancreatic duct diameter in those patients with an intact native sphincter of Oddi, these results were not statistically significant. In addition, there was no difference in those patients who had only a biliary sphincterotomy compared to those with both biliary and pancreatic sphincterotomies. Conclusion: Endoscopic sphincterotomy significantly decreases pancreatic duct dilation in response to secretin on S-MRCP. However, further studies are required to determine the effect of sphincterotomy on the amount of duodenal filling and the rate at which duodenal filling occurs. As S-MRCP is quickly becoming an increasingly utilized non-invasive method for documenting chronic pancreatitis, one must be aware of the absence of a functional pancreatic sphincter (s/p sphincterotomy) when reading S-MRCP, to avoid misinterpretation of pancreatic duct compliance.

Comparison of the Secretin Stimulated Endoscopic Pancreatic Function Test to Retrograde Pancreatogram

Duodenal intubation techniques with hormonal stimulation are the most accurate at diagnosing early chronic pancreatitis. Pancreatography (ERCP), the radiologic gold standard, can accurately diagnose chronic pancreatitis, but is expensive, may expose the patient to radiation, and/or induce acute pancreatitis. We have developed an endoscopic pancreatic function test (ePFT) that can assess pancreatic secretory function during upper endoscopy. We sought to determine the accuracy of the endoscopic secretin pancreatic function test using retrograde pancreatogram as the gold standard. Patients referred to The Pancreas Clinic for the evaluation and management of chronic abdominal pain and suspected chronic pancreatitis who had both endoscopic function testing and pancreatic duct imaging (ERCP) were studied. Pancreatograms were scored for duct morphologic characteristics (Cambridge classification) and compared to peak bicarbonate concentration in secretin stimulated duodenal juice. The ePFT consisted of a test dose of intravenous synthetic porcine secretin (0.2 microg), full-dose intravenous secretin (0.2 microg/kg) over 1 min, (3) upper endoscopy with moderate sedation, (4) gastric fluid aspirated and discarded, (5) duodenal fluid aspirations at 0, 15, 45, and 60 min after secretin injection, and (6) fluid analysis with lab autoanalyzer for bicarbonate concentration (historical normal cutpoint >80 mEq/L). Thirty-six patients had both the endoscopic function test and ERCP. Seventeen had chronic abdominal pain with normal pancreatograms, and nineteen had chronic abdominal pain with abnormal pancreatograms, consistent with chronic pancreatitis. The sensitivity and specificity of the endoscopic function test were 94% and 79%, respectively. The positive and negative predictive values were 80% and 94%, respectively. Overall agreement with ERCP was 86%. The ePFT with synthetic porcine secretin has excellent correlation with abnormal pancreatogram (chronic pancreatitis). Furthermore, a normal bicarbonate (negative function test, HCO(3) >80 mEq/L) essentially rules out chronic pancreatitis as a diagnostic cause of abdominal pain. Endoscopic pancreatic function testing may decrease the need for ERCP in patients with chronic abdominal pain.

Evaluation of the stimulating effect of a low dose of secretin compared to the standard dose on the exocrine pancreas with MRCP: preliminary results in normal subjects (MRCP quantification of secretin stimulation)

Secretin administration during MRCP improves depiction of pancreatic ducts and allows assessment of pancreatic exocrine secretions. However, secretin increases the cost of secretin-enhanced MRCP (S-MRCP). The aim of this study was to quantify using MRCP the stimulating effect of 0.3 CU/kg of secretin and to compare it to the standard dose (1 CU/kg). Ten healthy volunteers underwent four S-MRCP (two for each dose). Pancreatic exocrine secretions were quantified by pancreatic flow output (PFO) and total excreted volume (TEV), derived from a linear regression between MR calculated pancreatic exocrine volumes and time. Two readers analysed individually all sets of images. A linear increase of pancreatic exocrine volumes was observed after administration of both doses of secretin. Intra-individual and inter-observer differences were not statistically significant (P > 0.05). The mean PFO and TEV, given for reader 1 only, were, respectively, 6.9 +/- 1.5 mL/min and 103 +/- 26 mL for the standard dose and 6.1 +/- 1.2 mL/min and 84 +/- 19 mL for the dose of 0.3 CU/kg. Differences between PFO and TEV obtained with the two doses of secretin were statistically significant for both readers (P < 0.05). MRCP is a non-invasive, reproducible tool that allows quantification of pancreatic exocrine secretions during secretin stimulation. PFO and TEV calculated with the low dose were still in the range of previously reported reference values. The administration of 0.3 CU/kg of secretin can reduce significantly the cost of S-MRCP.

Atrial natriuretic factor negatively modulates secretin intracellular signaling in the exocrine pancreas

We previously reported that atrial natriuretic factor (ANF) stimulates pancreatic secretion through NPR-C receptors coupled to PLC and potentiates secretin response without affecting cAMP levels. In the present study we sought to establish the intracellular signaling mechanism underlying the interaction between both peptides. In isolated pancreatic acini 100 nM ANF abolished cAMP accumulation evoked by any dose of secretin. Lower doses of ANF (1 fM, 1 pM, 1 and 10 nM) dose dependently reduced EC50 secretin-evoked cAMP. Although ANF failed to affect cAMP stimulated by amthamine (selective H2 agonist) or isoproterenol (beta-adrenergic agonist), it abolished VIP-induced cAMP formation. ANF inhibitory effect was prevented by U-73122 (PLC inhibitor) and GF-109203X (PKC inhibitor) but unaltered by PKG and nitric oxide synthase inhibition, supporting that the PLC/PKC pathway mediated the effect. ANF response was mimicked by cANP (4-23 amide) and abolished by pertussis toxin, strongly supporting NPR-C receptor activation. In vivo studies showed that ANF at 0.5 microg x kg(-1) x h(-1) enhanced secretion stimulated by 1 U x kg(-1) x h(-1) secretin but at 1 and 2 microg x kg(-1) x h(-1) it abolished secretin response. However, ANF at such doses failed to modify the secretion evoked by carbachol or CCK. Present results show that ANF negatively modulated secretin secretory response and intracellular signaling through the activation of NPR-C receptors coupled to the PLC/PKC pathway. Furthermore, the finding that ANF also inhibited VIP-evoked cAMP supports a selective modulation of class II G-protein coupled receptors by ANF. Present findings suggest that ANF may play a protective role by reducing secretin response to avoid overstimulation.

Where Have All the Dreiling Tubes Gone?

The direct measurement of pancreatic function remains the best tool for diagnosing chronic pancreatitis, especially if imaging tests are normal or inconclusive. The most effective means of measuring pancreatic function is the standard hormone stimulation test using secretin. Traditionally, direct pancreatic function testing involves the fluoroscopic placement of an oroduodenal tube and collection of duodenal fluid containing pancreatic secretions after administration of a standardized dose of secretin and/or CCK. The test is time-consuming and tedious to perform, and placement of the oroduodenal tube is often difficult for the person performing the test and uncomfortable for the patient. Bicarbonate concentration typically has been measured by back-titration, requiring specialized equipment no longer found in most hospital clinical chemistry laboratories. For these reasons, the direct testing of pancreatic function after secretin stimulation has become a much admired but rarely performed test, currently done in only a few centers in the United States. In this issue of the Journal, Stevens et al. report on a cross-over study of secretin-stimulated endoscopic pancreatic function test (ePFT) and dreiling tube pancreatic function test (D-PFT) in healthy subjects and demonstrate that the accuracy of the ePFT is comparable to that of the D-PFT (17). They have demonstrated the relative simplicity and reliability of ePFT, bringing it closer to the diagnostic armamentarium of the practicing physician. We may have lost the Dreiling tube but, in its place, gained a "gold standard" which will be more widely used.

Effect of gastrointestinal hormone infusions on lower oesophageal competence of Rhesus monkeys

The lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.

Short report: autistic gastrointestinal and eating symptoms treated with secretin: a subtype of autism

Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which there is as yet no effective cure, and medical management remains a challenge for clinicians. The current report describes two patients affected by autistic disorder with associated gastrointestinal symptoms.They received multiple doses of intravenous secretin for a six-month period and were assessed with several specific outcome measures to evaluate drug effect.The administration of secretin led to some significant and lasting improvement in only one case.Gastroesophageal reflux may contribute to some of the behavioural problems and explain the effect of secretin since its suppressive effect on gastric secretion is well known. It is also true that autistic children with gastroesophageal reflux and a higher IQ could constitute a subtype which responds to secretin administration and that could be labelled as a "gastrointestinal subtype".

In children with autism, is intravenous secretin more effective than placebo in improving social skills, communication, behaviour or global functioning?

In children with autism, is intravenous secretin more effective than placebo in improving social skills, communication, behaviour or global functioning?

Secretin in a patient with treatment-resistant schizophrenia and prominent autistic features

Secretin, a gastrointestinal (GI) peptide, may offer therapeutic benefit in autism. Autistic features can also be present in schizophrenia and a recent study suggested a role for adjunctive secretin in treatment-resistant schizophrenia. The current report describes one patient with undifferentiated schizophrenia and prominent autistic features who received a single dose of secretin and demonstrated substantial yet transient improvement. The case illustrates the potential role of secretin as a novel adjunctive treatment strategy in schizophrenic patients with autistic features.

Secretin for refractory schizophrenia

In preliminary uncontrolled studies, intravenous injection of the gastrointestinal peptide secretin produced improvements in the symptoms of autism. Because of the phenotypic overlap between autism and some aspects of schizophrenia, we performed a pilot study of secretin for treatment refractory schizophrenia. Twenty-two patients were randomized to a single intravenous dose of porcine secretin or placebo. Patients were evaluated with the Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Clinical Global Impression Scale (CGI) at baseline, 2 days after secretin infusion and weekly for 4 weeks. There were no statistically significant differences between drug- and placebo-treated patients with repeated measures analysis of variance (ANOVA). However, several patients treated with secretin experienced clinically meaningful, but transient, reductions in symptoms and a greater percentage of patients treated with secretin were rated as improved with the CGI. Further study of brain hypocretins and molecules affecting this system are warranted in schizophrenia.

A Randomized, Double-Blind, Placebo-Controlled Trial of Porcine Versus Synthetic Secretin for Reducing Symptoms of Autism

To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms. Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy. Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups. No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately.

Amylase secretion from dispersed human pancreatic acini: neither cholecystokinin a nor cholecystokinin B receptors mediate amylase secretion in vitro.

In humans, cholecystokinin (CCK) stimulates pancreatic secretion, and CCK-A receptor antagonists prevent it in vivo. However, the human pancreas has been reported to express mainly CCK-B receptors. To elucidate this discrepancy. We prepared dispersed acini from human pancreas and examined whether various doses of CCK stimulated the release of amylase, in comparison with the effects of neuromedin C, carbamylcholine, and secretin. Human pancreatic acini did not respond to any dose of CCK or secretin. Amylase release was stimulated by carbamylcholine and neuromedin C dose-dependently and was inhibited by respective antagonists. The localizations of CCK receptors in the human duodenum were determined. High concentrations of CCK-A receptors were detected in the mucosa as well as in smooth muscle of the duodenum by microautoradiography. In conclusion, human pancreatic acinar cells are responsible for carbamylcholine and neuromedin C but not for secretin. Neither CCK-A nor CCK-B receptor mediates amylase release from human pancreatic acini in vitro. Pancreatic secretion in humans in vivo may be regulated indirectly by CCK (via CCK-A receptors).

Multiple doses of secretin in the treatment of autism: a controlled study

Dramatic effects on autistic behaviour after repeated injections of the gastrointestinal hormone secretin have been referred in a number of case reports. In the absence of curative and effective treatments for this disabling condition, this information has created new hope among parents. Although controlled studies on the effect of mainly one single dose have not documented any effect, many children still continue to receive secretin. Six children enrolled in a double‐blind, placebo‐controlled crossover study in which each child was its own control. Human synthetic secretin, mean dose 3.4 clinical units, and placebo were administered intravenously in randomized order every 4th wk, on three occasions each. The measurement instruments were the visual analogue scale (VAS) and the aberrant behaviour checklist (ABC). Statistically significant differences were found for placebo in 3 out of 6 children and for secretin in one child, using parental ratings only (VAS scores). Differences were small and lacked clinical significance, which was in accordance with the overall impression of the parents and teachers and visual inspection of graphs. Conclusion: In this placebo‐controlled study, multiple doses of secretin did not produce any symptomatic improvement.

Insulin inhibits secretin-induced pancreatic bicarbonate output via cholinergic mechanisms.

Exogenous insulin inhibits secretin-stimulated pancreatic bicarbonate output via a dose-dependent mechanism; this effect is prevented by pancreatic denervation. To investigate possible cholinergic mediation, we examined the effect of bethanechol on secretin-stimulated pancreatic secretion during euglycemic, hyperinsulinemic clamp. In four dogs with chronic pancreatic fistulas, euglycemic, hyperinsulinemic clamp (1.25 mU/kg/min) was begun after a 30-minute basal period; computer-assisted glucose administration maintained euglycemia. Control studies were performed with volume-matched and rate-matched vehicle infusion. After 1 hour, secretin infusion was begun at a dosage of 16 ng/kg/h; the dose was doubled every 30 minutes. The studies were then repeated during background bethanechol infusion (90 microg/kg/h) begun 30 minutes after clamp initiation. Pancreatic juice was analyzed for bicarbonate and protein; serum samples were analyzed for glucose and insulin. Exocrine outputs and serum glucose and insulin levels did not differ in the basal period. Insulin levels were significantly elevated during the euglycemic, hyperinsulinemic clamp (62 microU/mL versus 12 microU/mL; p < 0.01); glucose levels did not differ. As before, secretin-induced bicarbonate output was inhibited by euglycemic, hyperinsulinemic clamp. The inhibitory effect of insulin was reversed by bethanechol. Despite the euglycemic, hyperinsulinemic clamp, secretin-induced bicarbonate output was potentiated by bethanechol at higher secretin doses (p < 0.05). These data confirm that cholinergic mechanisms mediate insulin's inhibition of secretin-induced pancreatic bicarbonate output.

Captopril Inhibits Secretin-Induced Pancreatic Bicarbonate Output

Background. Renin–angiotensin systems function at both the organ and systemic levels. Previous studies suggest that angiotensin II (Ang II) stimulates pancreatic secretion in vitro. In contrast, in vivo studies suggest that Ang II inhibits pancreatic secretion. To further assess Ang II's influence on pancreatic secretion, we examined the effect of captopril on secretin-stimulated pancreatic output.Methods. After a 30-min basal period, four conscious dogs with chronic gastric and Herrera pancreatic fistulas received an intravenous bolus of captopril (0.1 mg/kg) followed by a continuous infusion (25 μg/kg/min). Control studies were performed with volume- and rate-matched saline infusion. After 1 h, secretin infusion was begun at 16 ng/kg/h, doubling the dose every 30 min. Pancreatic juice was analyzed for bicarbonate and protein. A paired t test was used to assess statistical significance.Results. When compared to controls, pancreatic bicarbonate outputs were lower during captopril administration; the difference between captopril and control was statistically significant at the highest secretin dose. Protein outputs also appeared lower during captopril administration, although these differences were not statistically significant.Conclusion. These data suggest that Ang II may augment secretin-induced pancreatic secretion. Further, the data seemingly refute the inhibitory role attributed to Ang II in earlier studies.