Conducted Vasodilation in Brain Parenchymal Arterioles is Impaired during Chronic Hypertension

Abstract

Brain parenchymal arterioles (PAs) are high resistance vessels that directly connect the pial surface vessels to the capillaries. We hypothesized that conduction of vasodilatory signals upstream in PAs is impaired during chronic hypertension, a consequence that may influence functional hyperemia and local control of blood flow in the brain. PAs from 18‐week old male stroke‐prone spontaneous hypertensive rats (SHRSP) and age‐matched Wistar rats (n=4‐8/group) were studied isolated and pressurized in an arteriograph system. As K+ is an important dilatory substance released locally during functional hyperemia that activates inward rectifier potassium channel (Kir), 15 mM KCl was applied locally by a micro‐pipette ejection system (400 ms, 20 psi) and lumen diameter of PAs recorded at local and conducted (600 µm proximally) sites. In Wistar rats, KCl dilated PAs at the local site close to their maximum diameter (59±5 in KCl vs. 70±5 µm in zero calcium; p>0.05). Local dilation to KCl was attenuated by the Kir blocker BaCl2 (30 µM), suggesting that KCl elicited vasodilation in PAs through Kir activation. Conduction of the vasodilatory signal was highly effective in PAs from Wistar rats, producing a conducted vasodilation that was 87±5 % of local. In SHRSP, both local and conducted responses to KCl were attenuated. The diameter of PAs from SHRSP in KCl locally was only 35±1 vs. 51±5 µm in zero calcium (p<0.05). Conduction of vasodilation was also less effective in SHRSP with only 64±6 % of the dilation conducted to the proximal site (p<0.05 vs. Wistar). In conclusion, conducted vasodilation in PAs is impaired during chronic hypertension that may adversely impact functional hyperemia and possibly lead to chronic ischemia in the brain. Supported by NIH PO1 HL095488.