Abstract P015: Bilateral Common Carotid Artery Stenosis in Hypertensive Rats Impairs Dilation in Penetrating Arterioles and Posterior Communicating Arteries

Hypertension and chronic cerebral hypoperfusion (CCH) are leading risk factors for cognitive impairment. We induced hypoperfusion in stroke prone spontaneously hypertensive rats (SHRSP) by bilateral carotid artery stenosis (BCAS) to create a novel, physiologically relevant model of cognitive impairment. We hypothesized that BCAS in SHRSP would impair endothelium dependent dilation and lead to outward remodeling of the penetrating arterioles (PAs) and posterior cerebral arteries (PCAs). The PAs are critical for maintaining parenchymal perfusion and controlling blood flow to the neurovascular unit, and the PCAs are integral in regulating the severity of CCH. Both artery types were studied by pressure myography and data are shown as mean±SEM, SHAM vs BCAS (an n =4 to 12 in each group) with p -6 M). BCAS impaired endothelial function in PAs, as evidenced by the abolition of the dilation (14±3.3% vs -10±4.7%) but did not significantly alter sodium nitroprusside induced dilation (60 ± 9.7% vs. 49 ± 6.4%). Inhibition of nitric oxide and prostacyclin production with L-NAME (100 μM) and indomethacin (10 μM), respectively, did not change dilation in either group. This suggests that endothelium-derived hyperpolarizing factor plays a role in PA dilation in SHRSP. PAs from BCAS rats had a reduced wall thickness (at 60 mmHg: 7±0.5 vs 5±0.6 μm), and wall-to-lumen ratio (at 60 mmHg: 0.10±0.002 vs 0.07±0.0001). BCAS increased wall stress in PAs (at 60 mmHg: 306±30.2 vs 427±48.3 dynes/cm 2 ). Endothelial dysfunction also was evident in the PCAs after BCAS (50 ± 13.0% vs 3 ± 14.9%) but the pattern of remodeling in these larger arteries was different. We did not observe a change in the wall thickness or wall-to-lumen ratio in PCAs after BCAS, but the lumen diameter was increased (at 80 mmHg: 105±7.7 vs 116±5.7 μm). These data suggest that endothelial dysfunction in the PAs and PCAs may worsen the severity of cerebral hypoperfusion and cognitive decline in SHRSP. The thinner walls in the PAs may also increase the risk of hemorrhage in the BCAS rats.