Matrix metalloproteinases contribute to endotoxin and interleukin-1β induced vascular dysfunction

摘要: Background and purpose: The acute vascular inflammatory dysfunction associated with endotoxaemia may reflect an imbalance between matrix metalloproteinases (MMPs) their natural inhibitors (TIMPs), induced by the endotoxin. This possibility was tested in rat aortic tissue. Experimental approaches: Tone phenylephrine rings measured after exposure vitro to ambient lipopolysaccharide (LPS) or proinflammatory cytokine interleukin-1b (IL-1b) for 6h, without MMP (doxycycline GM6001). Gelatinase activities, TIMP proteins contractility were aortae taken from rats 6h receiving LPS vivo. Key results: Inhibition of prevented loss phenylephrine–induced tone IL-1b. IL-1b also increased release MMP-2 activity In exposed vivo LPS, net gelatinase, MMP-9 activities TIMP-1 protein levels increased, whereas TIMP-4 reduced. These hypocontractile both KCl. Hypocontractility partially reversed doxycycline ex Conclusions Implications: ameliorate hyporeactivity either vitro. alters balance MMPs TIMPs, contributing which is inhibitors. Vascular are activated as a result IL-1b-induced stress contribute blood vessels vasoconstrictors. British Journal Pharmacology (2006) 149, 31–42. doi:10.1038/sj.bjp.0706823; published online 31 July 2006