ANTIHYPERTENSIVE TREATMENT WITH LISINOPRIL DECREASED STEROIDAL NA-PUMP INHIBITOR MARINOBUFAGENIN AND REDUCED ANXIETY IN DAHL-S RAT MODEL OF VASCULAR DEMENTIA

Age-associated increase in blood pressure (BP) and arterial stiffening contribute to vascular dementia. Dahl salt-sensitive rats (Dahl-S) exhibit a hypertensive response, remodeling of the vascular wall, cognitive impairment and increased anxiety with advancing age on a normal salt intake. Marinobufagenin (MBG), a novel pro-hypertensive factor which is stimulated by angiotensin II (AngII), is implicated in Dahl-S hypertension. We hypothesized that anti-hypertensive therapy would change the MBG level and affect behavior of adult hypertensive Dahl-S. Male Dahl-S were kept on a normal 0.5% NaCl intake (n=16) for the duration of the study. At 6 months of age, eight Dahl-S were treated with 15 mg/kg/day of Lisinopril, an ACE (ANGII converting enzyme) inhibitor, for 2 months. Eight rats served as a non-treated (vehicle-treated) control. Behavioral open field test (OFT), systolic BP (SBP) and urine MBG measurements were assessed at 6 months (baseline) and 8 months. Treatment with Lisinopril for 2 months did not affect normal body growth and significantly decreased SBP and MBG vs. baseline (Table). Distance travelled in the periphery of the open field was shorter, whereas distance travelled in the center was longer in Lisinopril group vs. their baseline (Table) indicating that anti-hypertensive treatment reduced the level of anxiety. Notably, that total distance travelled was unaffected by Lisinopril. SBP positively correlated with MBG (Figure 1), which supported the previous findings that MBG is a pro-hypertensive compound. Both SBP and MBG negatively correlated with the distance in the center of the open field (Figures 2, 3). MBG exhibited a strong correlation with the anxiety behavior marker.