Abstract P441: Accelerated Age-dependent Cardiovascular and Cognitive Decline in Dahl-S Rats is Associated with Elevated Levels of an Endogenous Na/K-ATPase Inhibitor

Abstract

Age-associated central arterial stiffening contributes to both cerebral arterial fibrosis and to cognitive impairment. Accelerated aging, accompanied by a gradual increase in blood pressure (BP) and aortic remodeling, occurs in Dahl-S rats (DSS) vs. normotensive Sprague-Dawley rats (S-D) counterparts even in the absence of a high salt intake. A novel pro-hypertensive factor marinobufagenin (MBG) is implicated in DSS hypertension. Here we determined whether an increase in MBG is also implicated in age-associated arterial remodeling in DSS. Methods: Life span was measured in 60 S-D and 78 DSS. BP, pulse wave velocity (PWV), behavioral water maze test, ANGII, MBG and aortic collagen were assessed in 3 and 9-mo S-D and DSS on a normal 0.5% NaCl intake. Results: Median life span in DSS is reduced by 50% vs. S-D (12±1 vs. 24±2 mo, p<0.01). At 3-mo DSS had higher SBP, PWV, ANGII, MBG, aortic and large cerebral arterial wall remodeling vs. 3-mo S-D (Table). Between 3 and 9-mo DSS, but not S-D, exhibited further increase in SBP, PWV, MBG and aortic collagen deposition. In a redundant place-cue version of the water maze test, 3-mo DSS demonstrated numerically impaired spatial hippocampal memory vs. 3-mo S-D, and by 9-mo, performance in DSS suggested the development of motor impairments, thus precluding an uncontaminated assessment of their spatial memory. Conclusions: In DSS high MBG occurred concurrently with fibrosis of aorta and large cerebral arteries and numerically impaired spatial memory. With advancing age of DSS further increase in BP, aortic stiffness and spatial learning/motor deficit occurred in context with an increase in MBG, which suggested an implication of MBG in these declines.