Evidence of early involvement of matrix metalloproteinase-2 in lead-induced hypertension.
Lead exposure increases blood pressure (BP) by unknown mechanisms. Many recent studies have shown the involvement of matrix metalloproteinases (MMPs) in hypertension, particularly MMP-2. In this work, we have examined whether MMP-2 levels increase with lead-induced increase in BP. We have also investigated whether doxycycline (an MMP inhibitor) affects these alterations. To this end, rats were exposed to lead (90 ppm) and treated with doxycycline or vehicle for 8 weeks. Similar aortic and whole blood lead levels were found in lead-exposed rats treated with either doxycycline or vehicle. Lead-induced increases in BP and aortic MMP-2 levels (activity, protein, and mRNA) were blunted by doxycycline. Doxycycline also prevented lead-induced increases in the MMP-2/TIMP-2 mRNA ratio. No significant changes in vascular reactivity or morphometric parameters were found. In conclusion, lead exposure increases BP and vascular MMP-2, which is blunted by doxycycline. This observation suggests that MMP-2 may play a role in lead-induced increases in BP.
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Elen
E
Rizzi
Michele M
MM
Castro
Karla
K
Fernandes
Fernando
F
Barbosa
Gabriel Maisonnave
GM
Arisi
Norberto
N
Garcia-Cairasco
Lusiane M
LM
Bendhack
Jose E
JE
Tanus-Santos
Raquel F
RF
Gerlach
D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006973:Hypertension / Q000503:physiopathology*; D007854:Lead / Q000097:blood / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D007854:Lead; D020778:Matrix Metalloproteinase 2; D004318:Doxycycline