Valsartan, a specific angiotensin II receptor blocker, inhibits pancreatic fluid secretion via vagal afferent pathway in conscious rats.
OBJECTIVE
The renin-angiotensin system (RAS) exists in the pancreas, but the role of RAS in the regulation of pancreatic exocrine secretion under physiological conditions has been little known. The present study addressed the RAS's effect on the pancreatic secretion by using valsartan, a specific angiotensin II receptor blocker, in conscious rats.


METHODS
Male Wistar rats prepared with pancreatic, biliary, duodenal and jugular vein cannulas were used. To examine the role of RAS in the pancreatic secretion, valsartan at 1, 5, or 25 mg/kg was administered into the duodenum via cannula, and volume of pancreatic juice and protein concentration were determined. In addition, to examine the role of RAS in hormone-stimulated pancreatic hypersecretion, pancreatic secretion was examined in response to stimulation of secretin or cholecystokinin after intraduodenal infusion of valsartan at 25 mg/kg. Furthermore, to examine the mechanism of action of RAS on pancreatic secretion, intravenous infusion of atropine or perivagal application of capsaicin was conducted and then the pancreatic secretion was examined following intraduodenal infusion of valsartan at 25 mg/kg.


RESULTS
Volume of pancreatic juice, but not protein output, significantly decreased after administration of valsartan. However, administration of valsartan did not exert significant effects on secretin- or cholesystokinin-stimulated pancreatic secretion. Treatment with atropine and perivagal application of capsaicin completely abolished the suppressive effect of valsartan on pancreatic juice secretion.


CONCLUSIONS
Present results suggest that RAS plays a stimulatory role in pancreatic juice secretion via cholinergic afferent pathway without affecting protein secretion and hormonally stimulated pancreatic secretion under physiological conditions.
The Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan. m-yamamo@med.uoeh-u.ac.jp
Mitsuyoshi
M
Yamamoto
Limin
L
Wei
Munenori
M
Otani
Masaru
M
Harada
Makoto
M
Otsuki
D000344:Afferent Pathways / Q000187:drug effects*; D000681:Amylases / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System; D012633:Secretin / Q000502:physiology; D018689:Sensory System Agents / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001639:Bicarbonates; D018727:Muscarinic Antagonists; D011506:Proteins; D018689:Sensory System Agents; D013777:Tetrazoles; D012633:Secretin; D001285:Atropine; D000068756:Valsartan; D002766:Cholecystokinin; D000681:Amylases; D014633:Valine; D002211:Capsaicin