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

1 In the rat balloon injury model, angiotensin-converting enzyme (ACE) inhi bitors prevent vascular remodelling by inhibiting angiotensin II generation and kinin breakdown. We investigated if ACE inhibition also prevents the s tructural 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 captopr il (120 mg kg(-1) per day). In addition, the effect of captopril on vascula r remodelling was tested in B-2(+/+) given the bradykinin (BK) BI receptor antagonist des-Arg(9)-[Leu(8)]BK (DALBK. 50 nmol kg(-1) per day, intraperit oneally) or the BK B-2 receptor antagonist D-Arg,[Hyp(3),Thi(5)D-Tic(7),Oic (8)]-BK (icatibant, 1 mu mol kg(-1) per day, intraperitoneally), and in Bz receptor gene knockout mice (B2(-/-)) 3 Interruption of blood flow resulted in carotid artery intimal hyperplasia and media thickening in untreated B-2(+/+), these responses being partiall y 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 kini n receptors nor disruption of the B-2 receptor gene altered the suppressive effect of captopril on media thickening. The protection of vascular wall s tructure was independent of the reduction in blood pressure by captopril. 4 These results demonstrate that kinins participate in the inhibitory effec t of captopril on intimal hyperplasia via B-1 and B-2 receptor signalling. Our findings may have important implications in treating vascular remodelli ng evoked by altered sheer stress conditions.