Please use this identifier to cite or link to this item:
|Type:||Artigo de periódico|
|Title:||Recombinant Human Matrix Metalloproteinase-2 Impairs Cardiovascular beta-Adrenergic Responses|
|Abstract:||Growing evidence supports the involvement of matrix metalloproteinases (MMPs) in the pathogenesis of many cardiovascular diseases. Particularly, imbalanced MMP-2 activity apparently plays a critical role in cardiovascular remodelling. While some studies have suggested that MMP-2 may affect the vascular tone and impair beta-adrenoreceptor function, no previous study has examined the acute haemodynamic effects of MMP-2. We examined the effects of recombinant human MMP-2 (rhMMP-2) administered intravenously to anaesthetized lambs at baseline conditions and during beta 1-adrenergic cardiac stimulation with dobutamine. We used 26 anaesthetized male lambs in two study protocols. First, rhMMP-2 (220 ng/kg/min. over 60 min.) or vehicle was infused in the lambs, and no significant haemodynamic changes were found. Therefore, we infused dobutamine at 5 mu g/kg/min. i.v. (or saline) over 180 min. in lambs that had received the same rhMMP-2 infusion preceded by doxycycline i.v. at 10 mg/kg (or saline). Plasma and cardiac MMP-2 levels were assessed by gelatin zymography, and gelatinolytic activity was assessed by spectrofluorimetry. Dobutamine decreased systemic vascular resistance index, and this effect was attenuated by rhMMP-2 infusion. Moreover, dobutamine increased the cardiac index and left ventricular dP/dtmax, and these effects were attenuated by rhMMP-2. The previous administration of doxycycline blunted rhMMP-2-induced changes in dobutamine responses. While the infusion of rhMMP-2 did not increase plasma and cardiac MMP-2 levels, it increased cardiac gelatinolytic activity, and doxycycline blunted this effect. Our findings show that rhMMP-2 exerts no major haemodynamic effects in lambs. However, rhMMP-2 impairs the responses elicited by activation of beta-adrenoreceptors.|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.