Metalloendopeptidases EC 3.4.24.15/16 regulate bradykinin activity in the cerebral microvasculature

American Journal of Physiology - Heart and Circulatory Physiology - Tập 284 Số 6 - Trang H1942-H1948 - 2003
M. Ursula Norman1, Rebecca A. Lew1, A. Ian Smith1, Michael J. Hickey2
1Baker Heart Research Institute, Melbourne, Victoria 8008; and
2Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, 3168, Australia

Tóm tắt

Bradykinin is a vasoactive peptide that has been shown to increase the permeability of the cerebral microvasculature to blood-borne macromolecules. The two zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) degrade bradykinin in vitro and are highly expressed in the brain. However, the role that these enzymes play in bradykinin metabolism in vivo remains unclear. In the present study, we investigated the role of EP 24.15 and EP 24.16 in the regulation of bradykinin-induced alterations in microvascular permeability. Permeability of the cerebral microvasculature was assessed in anesthetized Sprague-Dawley rats by measuring the clearance of 70-kDa FITC dextran from the brain. Inhibition of EP 24.15 and EP 24.16 by the specific inhibitor N-[1-( R, S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr- p-aminobenzoate (JA-2) resulted in the potentiation of bradykinin-induced increases in cerebral microvessel permeability. The level of potentiation was comparable to that achieved by the inhibition of angiotensin-converting enzyme. These findings provide the first evidence of an in vivo role for EP 24.15/EP 24.16 in brain function, specifically in regulating alterations in microvessel permeability induced by exogenous bradykinin.

Từ khóa


Tài liệu tham khảo

Abbott N, 1991, Cerebrovasc Brain Metab Rev, 3, 39

10.1023/A:1007074420772

10.1016/S0165-0173(97)00011-8

10.1146/annurev.ph.48.030186.001325

10.1590/S0100-879X2000000600008

10.1016/0196-9781(93)90185-J

10.1210/endo-116-4-1418

10.1111/j.1471-4159.1992.tb11021.x

10.1007/978-1-4615-4711-2_10

10.1161/01.HYP.37.1.110

10.1002/cne.1323

10.1161/01.STR.24.4.571

10.1111/j.1365-2826.1994.tb00576.x

10.1152/ajpheart.1985.248.5.H712

10.1042/bj2760583

10.1146/annurev.pa.35.040195.003335

10.1111/j.1432-1033.1983.tb07620.x

Regoli D, 1980, Pharmacol Rev, 32, 1

10.1111/j.1469-7793.2000.00177.x

10.1042/bj3450351

10.1210/er.2001-0032

Skidgel RA., 1992, J Cardiovasc Pharmacol, 20, S4, 10.1097/00005344-199200209-00003

10.1161/01.HYP.35.2.626

10.1016/0014-2999(95)00439-R

10.1523/JNEUROSCI.16-16-05049.1996

10.1038/jcbfm.1983.31

10.1016/0162-3109(96)00068-9

Wahl M, 1999, Acta Physiol Hung, 86, 155

10.1016/0197-0186(94)00114-A

10.1111/j.1476-5381.1991.tb12249.x

10.1080/026990596124395

Thông tin
Thông tin xuất bản

American Journal of Physiology - Heart and Circulatory Physiology

Tập 284 Số 6

H1942-H1948

Thông tin tác giả