Carotid Artery Stiffness and Elasticity in Angiotensin II Treated Mice

Hypertension, a risk factor for dementia, can impair the structure and function of cerebral arteries. Carotid arteries supply approximately 80% of the of blood required by the brain; increased stiffness and reduced distensibility in these arteries contribute to cerebrovascular disease. Angiotensin II (AngII)‐induced hypertension negatively affects the cerebral vasculature; it is possible that this is in part a response to increased carotid artery stiffness because stiffer arteries allow more of pulse pressure to be transmitted to the downstream vasculature. We hypothesized that AngII treatment in mice would lead to an increase in carotid artery wall stiffness, a loss of distensibility and impaired cognitive function. Sixteen‐week‐old C57BL/6 female mice were treated with AngII (1200 ng/kg/min via osmotic mini pump) for four weeks. Shams served as controls. Blood pressure was measured using tail‐cuff plethysmography. Barnes Maze was used to assess spatial memory and a nesting test was used to assess executive function. At euthanasia, arteries were isolated and mounted in a pressure myograph. To assess passive structure carotid arteries were incubated in Ca 2+ free physiological salt solution (PSS) containing EGTA (2μM) and sodium nitroprusside (100μM). A pressure‐response curve was constructed; the intraluminal pressure was increased from 3 to 140 mmHg in 20‐mmHg increments and lumen diameter (μm), outer diameter (μm), and wall thickness (μm) were measured at each pressure. These data were used to calculate wall‐to‐lumen ratio, distensibility, circumferential wall stress (dynes/cm 2 ), and wall strain. b‐coefficient, a measure of artery stiffness was calculated from stress/strain curves. Data are presented as means ± SEM (n=5–12). AngII infusion resulted in elevated systolic blood pressure (Sham: 142 ± 7; AngII 179 ± 7 mmHg; p<0.05). Barnes Maze tests showed that spatial memory was not impaired by AngII treatment (Sham: 25.2 ± 3.2; AngII 30.1 ± 3.4 seconds spent in target quadrant; p>0.05). Nesting test showed that executive function was impaired by Ang II treatment (Sham: 41.6 ± 7.7; AngII 10.5 ± 1.3 % nestlet shredded; p<0.05). There was no change in b‐coefficient in the AngII treated group (Sham: 4.91± 0.84; AngII 5.73 ± 1.20 p>0.05). Distensibility was also unaffected by Ang II treatment (Sham: 0.39 ± 0.01; AngII 0.39 ± 0.01; p>0.05). The change in executive function does not appear to be related to changes in carotid artery stiffness. Future studies will assess cerebral artery function. These data support the hypothesis that young female hypertensive mice are protected from changes in spatial memory, however, the impaired executive function is suggestive of initial negative changes in cognition. Support or Funding Information RO1‐HL‐137694‐01, AM Dorrance and WFJackson