This Article Full Text (PDF) References 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 Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Palei, A. C.T. Articles by Tanus-Santos, J. E. Search for Related Content PubMed PubMed Citation Articles by Palei, A. C.T. Articles by Tanus-Santos, J. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antibiotics Pulmonary Embolism Hazardous Substances DB DOXYCYCLINE Social Bookmarking                   What's this?

Hemodynamic Benefits of Matrix Metalloproteinase-9 Inhibition by Doxycycline During Experimental Acute Pulmonary Embolism

Department of Morphology, Estomatology and Physiology, Dental School of Ribeirao Preto, University of São Paulo, Ribeirao Preto

Rafael A.G. Zaneti

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto

Geisa M. Fortuna, MD

Department of Pharmacology, Faculty of Medical Sciences, State University of Campina, Campinas, Brazil

Raquel F. Gerlach, DDS, PhD

Department of Morphology, Estomatology and Physiology, Dental School of Ribeirao Preto, University of São Paulo, Ribeirao Preto

Jose E. Tanus-Santos, MD, PhD

Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, tanus{at}fmrp.usp.br

The authors examined whether acute pulmonary embolism (APE) increases lung matrix metalloproteinase (MMP)-2 and MMP-9 activities and whether inhibition of MMPs with doxycycline attenuates the hemodynamic changes associated with APE. Anesthetized male Wistar rats were monitored for mean arterial blood pressure (MAP) and heart rate (HR). Rats in the control group (n=5) received only saline IV; rats in the embolism (Emb) group (n=8) received saline IV followed 10 minutes later by an injection of Sephadex microspheres (9 mg/kg) IV; rats in the doxycycline (Doxy) group (n=4) received only doxycycline (30 mg/kg) IV, followed 10 minutes later by an injection of saline IV; rats in the Doxy + Emb group (n=8) received the same dose of doxycycline followed 10 minutes later by the same amount of microspheres described above. Lung samples were homogenized and assayed by SDS-polyacrilamide gel electrophoresis gelatin zymography to evaluate lung MMP-2 and MMP-9 activities. Saline or doxycycline produced no significant changes in MAP, HR, and in MMP-2 and MMP-9 activities. Conversely, lung embolization significantly reduced MAP by >32 mm Hg and HR by >90 bpm for more than 60 minutes, and increased MMP-9 activity by 43% (all p<0.05). No significant differences were observed in MMP-2 activity. However, lung embolization produced only transient hypotension in rats pretreated with doxycycline. In this group, MAP returned to baseline values 5 to 10 minutes after embolization. In addition, pretreatment with doxycycline blunted the increase in lung MMP-9 activity after lung embolization (p<0.05). This study demonstrates for the first time that MMP-9 inhibition with doxycycline attenuates APE-induced hemodynamic changes in the animal model examined. These findings indicate that MMP-9 activation plays a role in the pathophysiology of APE and suggest that pharmacologic strategies targeting specific MMPs with selective inhibitors may prevent the detrimental acute hemodynamic consequences of APE.

Angiology, Vol. 56, No. 5, 611-617 (2005)
DOI: 10.1177/000331970505600513


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. J. Greenlee, Z. Werb, and F. Kheradmand Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted Physiol Rev, January 1, 2007; 87(1): 69 - 98. [Abstract] [Full Text] [PDF]