PMID- 16166273 OWN - NLM STAT- MEDLINE DCOM- 20060123 LR - 20061115 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 315 IP - 3 DP - 2005 Dec TI - Expression of metallopeptidases and kinin receptors in swine oropharyngeal tissues: effects of angiotensin I-converting enzyme inhibition and inflammation. PG - 1065-74 AB - Angiotensin I-converting enzyme inhibitors (ACEi) cause both chronic and acute side effects, including rare but potentially life-threatening angioedema (AE). The main hypothesis to be tested in this study was that metallopeptidases and kinin receptors are present in oropharyngeal tissues and that their expression is modulated by ACEi and inflammation. Novel real-time polymerase chain reaction analysis was developed and allowed the relative quantification of tissue's gene expression for neprilysin, membrane-bound aminopeptidase P (mAPP), and both B1 and B2 kinin receptor subtypes in tongue, parotid gland, and laryngeal tissue (areas especially involved in the gravest clinical forms of AE) and in kidney in a porcine model (single injection or 7-day ACEi oral treatments applied or lipopolysaccharide injected as a positive inflammatory control). The results provide evidence of the expression and activities of kininases in oropharyngeal tissues in the swine. ACEi treatment modulated the expression of neutral endopeptidase and mAPP mRNA, but the corresponding enzyme activities and that of angiotensin I-converting enzyme (ACE) were generally stable in tissues. The 7-day ACEi treatment up-regulated both kinin receptor mRNAs in the oropharynx and the B1 receptor mRNA in the lingual vascular endothelium (immunohistochemistry). The inhibition of ACE in plasma is responsible for an accumulation of bradykinin and des-arginine9-bradykinin generated during activation of the contact system with glass beads. The expression of critical components of the kallikrein-kinin system in the oropharyngeal tissues supports the role of kinins in ACEi-induced AE. FAU - Moreau, Marie Eve AU - Moreau ME AD - Universite de Montreal, Faculte de Pharmacie, Room 3190, 2900 Blvd.Edouard-Montpetit, C.P. 6128, succ Centre-ville, Montreal, Quebec H3C 3J7, Canada. FAU - Dubreuil, Pascal AU - Dubreuil P FAU - Molinaro, Giuseppe AU - Molinaro G FAU - Chagnon, Miguel AU - Chagnon M FAU - Muller-Esterl, Werner AU - Muller-Esterl W FAU - Lepage, Yves AU - Lepage Y FAU - Marceau, Francois AU - Marceau F FAU - Adam, Albert AU - Adam A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050915 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Bradykinin) RN - 9007-41-4 (C-Reactive Protein) RN - EC 3.4.- (Metalloproteases) RN - EC 3.4.11.- (Aminopeptidases) RN - EC 3.4.11.9 (X-Pro aminopeptidase) RN - EC 3.4.15.1 (Peptidyl-Dipeptidase A) RN - EC 3.4.24.11 (Neprilysin) SB - IM MH - Aminopeptidases/analysis/genetics/metabolism MH - Angiotensin-Converting Enzyme Inhibitors/*pharmacology MH - Animals MH - C-Reactive Protein/analysis MH - Disease Models, Animal MH - Immunohistochemistry MH - *Inflammation MH - Male MH - Metalloproteases/analysis/genetics/*metabolism MH - Neprilysin/analysis/genetics/metabolism MH - Oropharynx/enzymology/*metabolism MH - Peptidyl-Dipeptidase A/analysis/*metabolism MH - RNA, Messenger/analysis MH - Random Allocation MH - Receptors, Bradykinin/analysis/drug effects/*metabolism MH - Sus scrofa MH - Up-Regulation EDAT- 2005/09/17 09:00 MHDA- 2006/01/24 09:00 CRDT- 2005/09/17 09:00 PHST- 2005/09/17 09:00 [pubmed] PHST- 2006/01/24 09:00 [medline] PHST- 2005/09/17 09:00 [entrez] AID - jpet.105.088005 [pii] AID - 10.1124/jpet.105.088005 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2005 Dec;315(3):1065-74. doi: 10.1124/jpet.105.088005. Epub 2005 Sep 15.