Increased contribution of L-arginine-nitric oxide pathway in aorta of micelacking the gene for vimentin

Experiments were designed to investigate endothelial function in the aorta of mice lacking the gene for the cytoskeleton protein vimentin (vim(-/-)). Rings with and without endothelium from wild-type (vim(+/+)), heterozygous (vim(+/-)), and homozygous (vim(-/-)) mice were suspended in organ chambers to record of changes in isometric tension. During phenylephrine contractio n, acetylcholine evoked comparable endothelium-dependent relaxations in the three groups. In the presence of N-omega-nitro-L-arginine, acetylcholine c aused endothelium-dependent contractions, which were greater in vim(-/-) th an in vim(+/+) and vim(+/-) aortas. Indomethacin did not affect relaxation to acetylcholine in vim(+/+) or in vim(+/-), but it significantly increased the maximal response in vim(-/-) (67 +/- 7 vs. 102 +/- 4%). Response to ac etylcholine in vim(-/-) aortas was not affected by cyclooxygenase type 2 in hibitor NS-398, the thromboxane receptor antagonist SQ-29,548, or superoxid e dismutase. Relaxations to sodium nitroprusside were not different between vim(+/+) and vim-mice and were not affected by cyclooxygenase inhibition. Cyclic guanosine monophosphate levels, which were increased to a comparable level by acetylcholine in vim(+/+) and vim(-/-), were augmented by indomet hacin in vim(-/-) aortas but not in vim(+/+) aortas. Expression of endothel ial nitric oxide synthase was not different between vim(+/+) and vim(-/-) p reparations. These results suggest that despite comparable endothelium-depe ndent responses to acetylcholine, endothelial cells from vim(-/-) mice rele ase a cyclooxygenase product that compensates the augmented contribution of nitric oxide.