title: Kinin B1 receptor upregulation by angiotensin II and endothelin-1 in rat vascular smooth muscle cells: receptors and mechanisms.
abstract: Oxidative stress upregulates the kinin B(1) receptor (B(1)R) in diabetes and hypertension. Since angiotensin II (ANG II) and endothelin-1 (ET-1) are increased in these disorders, this study aims at determining the role of these two prooxidative peptides in B(1)R expression in rat vascular smooth muscle cells (VSMC). In the A10 cell line and aortic VSMC, ANG II enhanced B(1)R protein expression in a concentration- and time-dependent manner (maximal at 1 μM and 6 h). In A10 cells, ANG II (1 μM) also increased B(1)R mRNA expression at 3 h and the activation of induced B(1)R with the agonist [Sar-d-Phe(8)]-des-Arg(9)-BK (10 nM, 5 min) significantly enhanced mitogen-activated protein kinase (MAPK1/2) phosphorylation. The enhancing effect of ANG II on B(1)R protein expression in A10 cells was normalized by the AT(1) (losartan) but not by the AT(2) (PD123319) receptor antagonist. Furthermore, it was inhibited by inhibitors of phosphatidylinositol 3-kinase (wortmannin) and NF-κB (MG132) but not of MAPK (PD098059). Whereas the ET(B) receptor antagonist (BQ788) had no effect, the ET(A) receptor antagonist (BQ123) blocked the effect of ANG II at 6-8 h but not at an early time point. BQ123 and BQ788 also blocked the increasing effect of ET-1 on B(1)R protein expression. Antioxidants (N-acetyl-l-cysteine and diphenyleneiodonium) abolished ANG II- and ET-1-increased B(1)R protein expression. In conclusion, B(1)R induction is linked to oxidative stress and activation of phosphatidylinositol 3-kinase and NF-κB. The newly synthesized B(1)R is functional and can activate MAPK signaling in VSMC. The effect of ANG II is mediated by the AT(1) receptor and the subsequent activation of ET(A) through ET-1 release.
authors.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3C 3J7.
authors.forename: Marielle
authors.initials: M
authors.lastname: Morand-Contant
authors.forename: Madhu B
authors.initials: MB
authors.lastname: Anand-Srivastava
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019332:Endothelin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D044022:Receptor, Endothelin A; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases