Hydralazine prevents angiotensin II-induced hypertension, cognitive dysfunction and blood brain barrier breakdown
Co-administration of hydralazine blunted the pressor response to angiotensin II and reduced systolic blood pressure in vehicle-infused mice at days 3 and 7 (Figure 3A). In the novel object recognition test to assess working memory, vehicle-infused mice spent a majority of time interacting with the novel object (Figure 3B and 3C) whereas angiotensin II-infused mice did not discriminate between novel and familiar objects (Figure 3B and 3C). Importantly, no such cognitive dysfunction was evident in angiotensin II-infused mice co-treated with hydralazine (Figure 3B and 3C). There was also evidence of memory impairment in a minority of the vehicle-infused mice treated with hydralazine (Figure 3C).
Angiotensin II increased IgG deposition in the hippocampus (Figures 3D-F) and cortex (Figures 3G-I), and this was prevented by co-treatment with hydralazine. Across all mice, IgG deposition was positively correlated in hippocampus (R2=0.13, P<0.05, Figure 3F) and cortex (R2=0.26, P<0.05, Figure 3I) with systolic blood pressure.