title: ACE inhibitor and AT1 antagonist stimulate duodenal HCO3- secretion mediated by a common pathway - involvement of PG, NO and bradykinin.
abstract: Recent study demonstrated that duodenal HCO3- secretion is affected by modulation of the renin-angiotensin system. We examined the effects of enalapril (angiotensin-converting enzyme (ACE) inhibitor) or losartan (angiotensin AT1 receptor antagonist) on duodenal HCO3- secretion in rats and investigated the mechanisms involved in the renin-angiotensin system-related HCO3- response. A proximal duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Enalapril increased the HCO3- secretion in a dose-dependent manner, with a decrease in arterial blood pressure (MBP), and these effects were significantly attenuated by pretreatment with indomethacin, L-NAME and FR172357 (a selective bradykinin B2 receptor antagonist). Although losartan alone did not affect the HCO3- secretion, despite reducing MBP, the agent dose-dependently increased the HCO3- secretion in the presence of angiotensin II, and this response was totally antagonized by prior administration of FR172357, indomethacin and L-NAME. Bradykinin also dose-dependently increased the HCO3- secretion with no change in MBP, though transient, and again the effects were blocked by indomethacin, L-NAME and FR172357. Both prostaglandin (PG) E2 and the nitric oxide (NO) donor NOR-3 also increased the HCO3- secretion, the latter effect being inhibited by indomethacin. These results suggest that both an ACE inhibitor and AT1 antagonist (in the presence of angiotensin II) increase duodenal HCO3- secretion via a common pathway, involving bradykinin, NO and PGs. It is also assumed that bradykinin releases NO locally, which in turns stimulates HCO3- secretion mediated by PGs.
authors.affiliation: Department of Pharmacology and Experimental Therapeutic Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Aihara
authors.forename: S
authors.initials: S
authors.lastname: Kagawa
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001639:Bicarbonates; D011453:Prostaglandins; D009569:Nitric Oxide; D004656:Enalapril; D019001:Nitric Oxide Synthase; D019808:Losartan; D015232:Dinoprostone; D001920:Bradykinin