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Participation of kinins in the captopril‐induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse
Author(s) -
Emanueli Costanza,
Salis Maria Bonaria,
Figueroa Carlos,
Chao Julie,
Chao Lee,
Gaspa Leonardo,
Capogrossi Maurizio C,
Madeddu Paolo
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703388
Subject(s) - kinin , captopril , bradykinin , icatibant , medicine , endocrinology , receptor antagonist , ace inhibitor , angiotensin converting enzyme , angiotensin ii , intimal hyperplasia , chemistry , antagonist , receptor , pharmacology , blood pressure , smooth muscle
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. 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 8 ]‐BK (DALBK, 50 nmol kg −1 per day, intraperitoneally) or the BK B 2 receptor antagonist D‐Arg,[Hyp 3 ,Thi 5 D‐Tic 7 ,Oic 8 ]‐BK (icatibant, 1 μmol kg −1 per day, intraperitoneally), and in B 2 receptor gene knockout mice (B 2 −/− ). 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 B 2 −/− ( 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. 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.British Journal of Pharmacology (2000) 130 , 1076–1082; doi: 10.1038/sj.bjp.0703388