Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury

Timothy A. Sutton, K. J. Kelly, Henry E. Mang, Zoya Plotkin, Ruben M. Sandoval, Pierre C. Dagher

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Tetracyclines exhibit significant anti-inflammatory properties, inhibit matrix metalloproteinases (MMPs), and are protective in models of ischemia-reperfusion injury (IRI). Both inflammatory cascades and MMP activation have been demonstrated to modulate microvascular permeability. Because increased microvascular permeability occurs during IRI in a variety of organ systems including the kidney, we hypothesized that minocycline, a semisynthetic tetracycline, would diminish microvascular leakage during renal IRI. To test this hypothesis, we used intravital 2-photon microscopy to examine leakage of fluorescent dextrans from the vasculature in a rodent model of IRI. Minocycline significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Although minocycline diminished leukocyte accumulation in the kidney following ischemia, areas of leukocyte accumulation did not correlate with areas of microvascular permeability in either the saline- or minocycline-pre-treated animals. Minocycline diminished the perivascular increase in MMP-2 and MMP-9, as well as the increase in MMP-2 activity 24 h after ischemia. ABT-518, a specific inhibitor of MMP-2 and MMP-9, also significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Our results indicate that minocycline mitigates the renal microvascular permeability defect following IRI. This effect is spatially distinct from the effect of minocycline on leukocyte accumulation and may be related to diminished activity of MMPs on the integrity of the perivascular matrix.

Original languageEnglish (US)
Pages (from-to)F91-F97
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 2005

Keywords

  • Kidney
  • Matrix metalloproteinase
  • Tetracycline
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology

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