Endothelium-independent flow-induced dilation in the mouse carotid artery.
BACKGROUND
We investigated the locus of flow regulation of vascular tone in carotid arteries of C57 Bl/6 and eNOS(-/-) mice.


METHODS
Arterial segments (2-3 mm) were mounted in a perfusion myograph and preconstricted with 1 muM phenylephrine before monitoring flow-induced changes in lumen diameter.


RESULTS
Both control and eNOS(-/-) mice demonstrated flow-dependent relaxation. This response was not attenuated by the NO synthase antagonist L-NAME, the cyclooxygenase inhibitor indomethacin, the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), the adenylate cyclase inhibitor Rp-8-Br-cAMPs, integrin-binding RGD peptides, or by removal of the endothelium. Hypoxia, a physiological stimulus known to alter endothelium-dependent flow regulation of vascular tone, also failed to attenuate the observed flow-mediated dilation.


CONCLUSIONS
These findings indicate the existence of a previously unidentified endothelium-independent mechanism of flow-induced dilation in the carotid artery. Further investigations to identify the mechanisms that underlie this response may provide novel therapeutic directions in the treatment of disorders characterized by abnormal flow regulation of vascular tone.
Quan
Adrian
A
Toronto General Hospital, Toronto, Canada.
Ward
Michael E
ME
Kulandavelu
Shathiyah
S
Adamson
S Lee
SL
Langille
B Lowell
BL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
C494582:1H-(1,2,3)oxadiazolo(4,4-a)quinoxalin-1-one; D016861:Cyclooxygenase Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D014665:Vasodilator Agents; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin