Abstract T P416: Bilateral Common Carotid Artery Stenosis in Normotensive Rats Impairs Short-Term Memory and Dilation in Penetrating Arterioles

Chronic cerebral hypoperfusion (CCH) is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral common carotid artery stenosis (BCAS) is a physiologically relevant model of CCH. We hypothesized that BCAS in Wistar Kyoto (WKY) rats would impair cognitive function, we further proposed that in an effort to compensate for the reduced blood flow BCAS would lead to increased dilation and outward remodeling in the penetrating arterioles (PAs). Data are shown as mean±SEM, SHAM vs BCAS. BCAS reduced pial artery perfusion in 20-week-old male WKY rats (469±8 vs 299±21 perfusion units p<0.05). Short-term memory, evaluated by novel object recognition testing, was impaired (novel exploration quotient: 0.62±0.09 vs 0.46±0.14, p<0.05). PA reactivity and structure were assessed by pressure myography. There was no difference in myogenic tone between the groups [SHAM (n=4) and BCAS (n=7), % average tone: 34.5±9.8]. Contrary to our hypothesis, BCAS impaired endothelial function of PAs from 28-29 weeks old WKY rats, as evidenced by reduced dilation to endothelium dependent dilator carbachol (% change in diameter from baseline at 10-5M: 7.0±4.1 vs -1.8±5.6, Student’s t-test p<0.05). Inhibition of nitric oxide and prostacyclin production did not change the response to carbachol or the myogenic tone in either group. This suggests that endothelium derived hyperpolarizing factor (EDHF) plays a role in PA dilation in the SHAM rats; the role of EDHF in the PAs from the BCAS rats remains to be investigated but the lack of dilation to carbachol under any conditions suggests a general impairment in endothelial function. There was no difference in the PA passive structure between the groups. Work from our lab suggests that CCH leads to outward remodeling of the posterior communicating artery (PCA). Lumen diameter of the PCAs is important in regulating the severity of CCH. BCAS increased lumen diameter, wall-to-lumen ratio and distensibility of the PCAs (two-way ANOVA, p<0.05). These data suggest that BCAS impairs short-term memory, and may contribute to impaired endothelium dependent dilation of the PAs. BCAS in normotensive WKY rats also leads to outward remodeling in the PCAs but it did not alter PA passive structure.