IMPAIRED FLOW-INDUCED DILATION IN MESENTERIC RESISTANCE ARTERIES FROMMICE LACKING VIMENTIN

The intermediate filament vimentin might play a key role in vascular r esistance to mechanical stress. We investigated the responses to press ure (tensile stress) and flow (shear stress) of mesenteric resistance arteries perfused in vitro from vimentin knockout mice, Arteries were isolated from homozygous (Vim(-/-), n = 14) or heterozygous vimentin-n ull mice (Vim(+/-), n = 5) and from wild-type littermates (Vim(+/+), n = 9). Passive arterial diameter (175 +/- 15 mu m in Vim(+/+) at 100 m mHg) and myogenic tone were not affected by the absence of vimentin, F low-induced (0-150 mu l/min) dilation (e.g., 19 +/- 3 mu m dilation at 150 mmHg in Vim(+/+)) was significantly attenuated in Vim(-/-) mice ( 13 +/- 2 mu m dilation, P < 0.01), Acute blockade of nitric oxide synt hesis (N-G-nitro-L-arginine, 10 mu M) significantly decreased flow-ind uced dilation in both groups, whereas acute blockade of prostaglandin synthesis (indomethacin, 10 mu M) had no significant effect, Mean bloo d pressure, in vivo mesenteric blood flow and diameter, and mesenteric artery media thickness or media to lumen ratio were not affected by t he absence of vimentin. Thus, the absence of vimentin decreased select ively the response of resistance arteries to flow, suggesting a role f or vimentin in the mechanotransduction of shear stress.