Faculty Collaboration Database

Bradykinin B(1) receptor mediates inhibition of neointima formation in rat artery after balloon angioplasty. Hypertension 2000 Sep;36(3):364-70

Date

09/16/2000

Pubmed ID

10988266

DOI

10.1161/01.hyp.36.3.364

Scopus ID

2-s2.0-0033812122 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

We evaluated the effects of the kallikrein-kinin system on the proliferation and migration of primary cultured vascular smooth muscle cells (VSMCs) in vitro and neointima formation in balloon-injured rat carotid arteries in vivo. In cultured rat VSMCs, tissue kallikrein inhibited cell proliferation, and this inhibitory effect was blocked by Sar-Tyr-Aca(epsilon)-Lys [D-betaNal(7), Ile(8)]-des-Arg(9)-bradykinin, a bradykinin B(1) receptor antagonist, and by icatibant, a bradykinin B(2) receptor antagonist. Platelet-derived growth factor significantly increased the expression of the B(1) receptor but not the B(2) receptor in VSMCs. Platelet-derived growth factor-induced cell migration was significantly attenuated by des-Arg(9)-bradykinin and to a lesser degree by bradykinin. Endogenous B(1) receptor mRNA increased in rat carotid arteries after balloon angioplasty. After local delivery of adenovirus carrying the human tissue kallikrein gene into the rat carotid artery, we observed a 54% reduction in the intima/media ratio at the injured site compared with the control ratio (n=7, P:<0.01). Administration of the B(1) receptor antagonist via minipumps blocked the protective effect of kallikrein and partially reversed the intima/media ratio toward the control ratio. Kallikrein gene delivery results in the regeneration of endothelium compared with the control groups, and the B(1) receptor antagonist abolished this effect. Nitrite/nitrate, cGMP, and cAMP levels in balloon-injured arteries significantly increased after kallikrein gene delivery, whereas the B(1) receptor antagonist abolished these increases (n=4 or 5, P:<0.05). These results indicate that the B(1) receptor contributes to the reduction of neointima formation via the promotion of reendothelialization and inhibition of VSMC proliferation and migration through NO-cGMP and cAMP signaling pathways. This study provides significant implications in treating restenosis after revascularization.

Author List

Agata J, Miao RQ, Yayama K, Chao L, Chao J

MESH terms used to index this publication - Major topics in bold

Adenoviridae
Animals
Bradykinin Receptor Antagonists
Carotid Arteries
Carotid Artery Injuries
Catheterization
Cell Division
Cell Movement
Constriction, Pathologic
Genetic Vectors
Male
Rats
Rats, Sprague-Dawley
Receptor, Bradykinin B1
Receptor, Bradykinin B2
Receptors, Bradykinin
Reverse Transcriptase Polymerase Chain Reaction
Tissue Kallikreins
Transfection
Tunica Intima