Participation of kinins in the captopril-induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse

Costanza Emanueli, Maria Bonaria Salis, Carlos Figueroa, Julie Chao, Lee Chao, Leonardo Gaspa, Maurizio C. Capogrossi, Paolo Madeddu

Research output: Contribution to journalArticle

Abstract

1. In the rat balloon injury model, angiotensin-converting enzyme (ACE) inhibitors prevent vascular remodelling by inhibiting angiotensin II generation and kinin breakdown. We investigated if ACE inhibition also prevents the structural vascular responses to disruption of carotid artery blood flow and if kinin potentiation plays a role in such a protection. 2. Morphometric analysis of the structural alterations caused by ligation of the left carotid artery was performed 14 days after surgery in J129Sv wild-type mice (B 2(+/+)) drinking normal tap water or water containing captopril (120 mg kg -1 per day). In addition, the effect of captopril on vascular remodelling was tested in B 2(+/+) given the bradykinin (BK) B 1 receptor antagonist des-Arg 9-[Leu(X)]-BK (DALBK, 50 nmol kg -1 per day, intraperitoneally) or the BK B 2 receptor antagonist D-Arg,[Hyp 3,Thi 5D-Tic 7,Oic 8]-BK (icatibant, 1 μmol kg -1 per day, intraperitoneally), and in B 2 receptor gene knockout mice (B 2(-/-)). 3. Interruption of blood flow resulted in carotid artery intimal hyperplasia and media thickening in untreated B 2(+/+), these responses being partially suppressed by captopril. The inhibition of intimal thickening exerted by captopril was reduced in B 2(+/+) given DALBK or icatibant (P <0.05 for both comparisons) as well as in B1 (P <0.05). Neither antagonism of kinin receptors nor disruption of the B 2 receptor gene altered the suppressive effect of captopril on media thickening. The protection of vascular wall structure was independent of the reduction in blood pressure by captopril. 4. These results demonstrate that kinins participate in the inhibitory effect of captopril on intimal hyperplasia via B 1 and B 2 receptor signalling. Our findings may have important implications in treating vascular remodelling evoked by altered shear stress conditions.

Original languageEnglish
Pages (from-to)1076-1082
Number of pages7
JournalBritish Journal of Pharmacology
Volume130
Issue number5
Publication statusPublished - 2000

Keywords

  • Angiotensin converting enzyme inhibitors
  • Intimal hyperplasia
  • Kinins
  • Knockout mice
  • Nitric oxide
  • Receptor antagonists

ASJC Scopus subject areas

  • Pharmacology

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