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This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/H684    most recent 00538.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by He, J. Z. Articles by Ward, M. E. Search for Related Content PubMed PubMed Citation Articles by He, J. Z. Articles by Ward, M. E.

Induction of matrix metalloproteinase-2 enhances systemic arterial contraction after hypoxia

¹Terrence Donnelly Laboratories, Division of Respirology and Department of Critical Care, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada; ²Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; ³Departments of Obstetrics/Gynaecology and Physiology, University of Alberta, Edmonton, Alberta, Canada; ⁴Department of Medicine, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada; and ⁵Laboratory for Behavioural Genetics, Riken Brain Science Institute, Wako City, Japan

Submitted 25 May 2006 ; accepted in final form 11 September 2006

This study was carried out to determine the role of increased vascular matrix metalloproteinase-2 (MMP-2) expression in the changes in systemic arterial contraction after prolonged hypoxia. Rats and mice were exposed to hypoxia (10% and 8% O₂, respectively) or normoxia (21% O₂) for 16 h, 48 h, or 7 days. Aortae and mesenteric arteries were either mounted in organ bath myographs or frozen in liquid nitrogen. MMP-2 inhibition with cyclic CTTHWGFTLC (CTT) reduced contraction to phenylephrine (PE) in aortae and mesenteric arteries from rats exposed to hypoxia for 7 days but not in vessels from normoxic rats. Similarly, CTT reduced contraction to Big endothelin-1 (Big ET-1) in aortae from rats exposed to hypoxia for 7 days. Responses to PE were reduced in hypoxic MMP-2^–/– mice compared with MMP-2^+/+ mice. Increased contraction to Big ET-1 after hypoxia was observed in MMP-2^+/+ mice but not in MMP-2^–/– mice. Rat aortic MMP-2 and membrane type 1 (MT1)-MMP protein levels and MMP activity were increased after 7 days of hypoxia. Rat aortic MMP-2 and MT1-MMP mRNA levels were increased in the deep medial vascular smooth muscle. We conclude that hypoxic induction of MMP-2 expression potentiates contraction in systemic conduit and resistance arteries. This may preserve the capacity to regulate the systemic circulation in the transition between the alterations in vascular tone and structural remodeling that occurs during prolonged hypoxic epochs.

vascular smooth muscle; endothelium; endothelin; vascular remodeling

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