Bradykinin responses in experimental vein grafts
Bradykinin receptor subtype expression (B1 and B2) is known to be modulated by tissue injury. Reversed vein arterial grafts undergo structural, biochemical, and functional changes, one of which is a reduced sensitivity to bradykinin. This study examines bradykinin receptor expression in mature experimental vein graft tissue in the rabbit model. Thirteen New Zealand White rabbits underwent either common carotid interposition bypass grafting (n = 8) using the ipsilateral external jugular vein or excision of the vein as a control (n = 8, 5 rabbits). Grafts were harvested at 28 days. Standard isometric tension studies on rings from either vein grafts or control veins were performed. Cumulative dose-response curves to bradykinin (10-12 to 10-5 M), Lys-bradykinin (10-12 to 10-5 M) and des-Arg9-bradykinin (10-12 to 3 x 10-5 M) were obtained. Following incubation with either d-Arg, [Hyp3, Thi5,8, d-Phe7] bradykinin (DAHBK, B2 antagonist; 10-5 M), des-Arg9 [Leu8] bradykinin (DALBK, B1 antagonist; 10-5 M), or captopril (10-5 M), dose-response curves to bradykinin were repeated. All results are expressed as the mean ± SEM of the pD2 defined as -log10 [ED50 (M)]. Responses to bradykinin and Lys-bradykinin were greatly decreased in the vein grafts compared with the control veins. Des-Arg9-bradykinin had a negligible response in the control veins but did produce a sigmoid dose-response curve in vein grafts (pD2, 6.34 ± 0.17). The bradykinin response was antagonized by DAHBK in the control veins (pD2, 6.76 ± 0.28 vs. 8.48 ± 0.11) but not in the vein grafts (pD2, 5.55 ± 0.18 vs. 5.56 ± 0.20). DALBK and captopril did not affect the response of either tissue to bradykinin. It is concluded that when a vein is transplanted into the arterial circulation, there is an up-regulation of a putative B1 contractile response coupled to a decreased B2 contractile response. This may reflect the tissue's response to either inflammatory or mechanical injury in this model of experimental vein bypass grafting.
Massey, MF; Davies, MG; Klyachkin, ML; Schwartz, LB; Barber, L; McCann, RL; Hagen, PO
Journal of Vascular Medicine and Biology
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