QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.088005v1 315/3/1065    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moreau, M. E. Articles by Adam, A. Search for Related Content PubMed PubMed Citation Articles by Moreau, M. E. Articles by Adam, A.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Expression of Metallopeptidases and Kinin Receptors in Swine Oropharyngeal Tissues: Effects of Angiotensin I-Converting Enzyme Inhibition and Inflammation

Faculté de Pharmacie (M.E.M., G.M., A.A.), Faculté des Arts et des Sciences, Département de Mathématiques et de Statistique (M.C., Y.L.) and Faculté de Médecine Vétérinaire (P.D.), Université de Montréal, Montréal, Québec, Canada; Centre Hospitalier Universitaire de Québec, Centre de Recherche, Québec, Canada (F.M.); and Institute of Biochemistry II, Johann Wolfgang Goethe University School of Medicine, Frankfurt, Germany (W.M.-E.)

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.

Address correspondence to: Dr. Albert Adam, Université de Montréal, Faculté de Pharmacie, Room 3190, 2900 Blvd.Édouard-Montpetit, C.P. 6128, succ Centre-ville, Montréal, Québec H3C 3J7, Canada. E-mail: albert.adam{at}umontreal.ca

This article has been cited by other articles:

				M. E. Moreau, M.-T. Bawolak, G. Morissette, A. Adam, and F. Marceau Role of Nuclear Factor-{kappa}B and Protein Kinase C Signaling in the Expression of the Kinin B1 Receptor in Human Vascular Smooth Muscle Cells Mol. Pharmacol., March 1, 2007; 71(3): 949 - 956. [Abstract] [Full Text] [PDF]