Critical Role of Matrix Metalloproteinase-9 in Acute Cold Exposure–Induced Stroke in Renovascular Hypertensive Rats

Our objectives are to investigate the role of MMP-9 in cold exposure–induced stroke and assess the preventive effect of doxycycline, a total of 200 rats were assigned to a control group, sham group, 2-kidney, 2-clip (2K–2C) group, and doxycycline-received 2K-2C group (2K–2C + doxy) (N = 50, each), and subsequently, each group were randomly assigned to 2 groups: acute cold exposure (ACE) and nonacute cold exposure (NACE) (N = 25, each). After the blood pressure was stabilized, rats were maintained on a 12-h light (22°C)/dark (4°C) cycle (ACE group) or a 12-h light (22°C)/dark (22°C) cycle (NACE group) for 3 cycles. The results showed that ACE upregulated Ang II and MMP-9 protein levels in brains and aortas and considerably enhanced stroke incidence in 2K–2C rats. In contrast, doxycycline treatment prevented upregulation of MMP-9 protein expression and activity in brains and aortas in response to ACE and significantly decreased stroke incidence. These findings suggest that cold exposure–induced MMP-9 via activation of RAS might play a critical role in the initiation of cold exposure–induced stroke during chronic hypertension and doxycycline shows protective effects against cold exposure–induced stroke.