Aging impairs myogenic adaptation to pulsatile pressure in mouse cerebral arteries (1079.7)

Abstract

Stability of myogenic tone of cerebral arteries is essential for adequate control over penetration of pressure (P) waves into the distal portion of the cerebral microcirculation (the resistance to flow is dominated by the fourth power of the internal vessel radius). Because aging promotes cerebromicrovascular injury, we tested the hypothesis that aging alters the myogenic response. P‐induced constriction of cannulated middle cerebral arteries (MCA) isolated from young (3 mo) and aged (24 mo) mice was assessed. Both young and aged MCAs developed similar myogenic tone in response to stepwise, steady‐state increases in intraluminal P. Young MCAs exhibited significant myogenic adaptation to sinusoidal pulsatile P (amplitude: 40 mmHg, freq:450/min). While in myogenically inactive MCAs each P pulse elicited a ~7% distension in synchrony with the pulsatile P, in young myogenically active MCAs the amplitude of the diameter changes induced by the P pulses in the autoregulated P range was significantly attenuated (~2%). The mean P‐myogenic tone curve was similar in young MCAs exposed to constant and pulsatile P. In aged MCAs the cyclic changes in diameter induced by the P pulses were increased (~4%) and development of myogenic tone in response to pulsatile P was impaired. Collectively, aging impairs myogenic adaptation of cerebral arteries to pulsatile P, which likely promotes the development of cerebral microbleeds and BBB disruption by allowing high P to penetrate the distal portion of the cerebral microcirculation.Grant Funding Source: Supported by TÁMOP 4.2.4.A/2‐11‐1‐2012‐0001,SROP‐4.2.2.A‐11/1/KONV‐2012‐0024 and 0017,OTKA K‐108444