ACE inhibition by enalaprilate stimulates duodenal mucosal alkaline secretion via a bradykinin pathway in the rat.
The effects of enalaprilate on duodenal mucosal alkaline secretion (in situ titration) and mean arterial blood pressure were investigated in chloralose-anesthetized male rats. A bolus injection of enalaprilate (0.7 mg/kg intravenously) increased alkaline secretion by about 60%, and this response was resistant to guanethidine (5 mg/kg intravenously), splanchnicotomy, and vagotomy. Furthermore, angiotensin II infusion (0.25-2.5 microg/kg/hr intravenously) following the administration of enalaprilate failed to influence this response. Bradykinin (10(-6)-10(-4) M) applied topically to the serosal surface of the duodenal segment under study increased dose-dependently the duodenal mucosal alkaline secretion, an effect that could be blocked by the selective bradykinin receptor subtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response to enalaprilate. These data suggest that enalaprilate increases duodenal mucosal alkaline secretion via a local bradykinin pathway involving receptors of the bradykinin receptor subtype-2 antagonist, rather than by blockade of endogenous angiotensin II or by central autonomic neural regulation.
Chen
L
L
Department of Clinical Pharmacology, Göteborg University, Sweden.
Holm
M
M
Fändriks
L
L
Pettersson
A
A
Johansson
B
B
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D015773:Enalaprilat / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000502:physiology; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001639:Bicarbonates; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin; D000804:Angiotensin II; C065679:icatibant; D015773:Enalaprilat; D001920:Bradykinin