Abstract TP450: Angiotensin II-induced Hypertension is Associated With Parenchymal Arteriole and Posterior Cerebral Artery Remodeling and Reduced Cerebral Perfusion

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Hypertension can cause inward artery remodeling, artery rarefaction, increased vascular resistance and blood brain barrier (BBB) breakdown. These conditions increase the risk of stroke and dementia. The differential effects of Ang II-induced hypertension on the posterior cerebral artery (PCA) and parenchymal arterioles (PAs) have not been investigated. The PAs serve as bottlenecks for the perfusion of the cortex and are important in determining the outcome of stroke. We hypothesized that Ang II-induced hypertension would cause inward remodeling of the PAs and PCAs, artery rarefaction, and blood brain barrier breakdown. PAs and PCAs were collected from 20-week-old male C57Bl/6 mice to assess structure by pressure myography. Data collected at an intraluminal pressure of 60mmHg are presented as mean ± SEM; Sham (n=5) vs. Ang-II (n=5; 800ng/kg/day for 4 weeks). Ang II increased systolic (148 ± 4 vs 176 ± 6mmHg) and diastolic (115 ± 4 vs. 144 ± 6mmHg) blood pressures (p < 0.05). In the PAs, the lumen diameter (37 ± 3 vs. 22 ± 3μm), wall area (830 ± 118 vs. 632 ± 53μm2) and wall stress (199 ± 24 vs 98 ± 22dynes/cm2) were reduced in hypertensive mice (p<0.05). Preliminary studies suggest that Ang II-induced hypertension also impairs myogenic tone and endothelium-dependent dilation in the PAs. In the PCAs, hypertension decreased the lumen diameter (130 ± 5 vs. 97 ± 7μm, p < 0.05). The wall/lumen ratio was increased (0.08 ± 0.01 vs 0.14 ± 0.03) while wall stress (362 ± 28 vs 264 ± 33dynes/cm2) was reduced (p < 0.05). The decreased cerebral perfusion (836 ± 50 vs. 596 ± 83 perfusion units; p < 0.05) is due primarily to artery remodeling and not to artery rarefaction (10.8 ± 0.9 vs 9.5 ± 0.9 number of vessels/area; p > 0.05). Ang II-induced artery remodeling was not associated with increased BBB permeability (2 ± 1 vs 3 ± 1 % extravasation Evans Blue; p > 0.05). Our results suggest that Ang II-induced hypertension results in remodeling of the PCA and PAs associated with decreased cerebral perfusion; this could have detrimental effects on neuronal function increasing the risk of vascular dementia and stroke.

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