Flow stimulates endothelial cells to release a nitrovasodilator that is potentiated by reduced thiol.
We designed a novel system to study flow-mediated endothelium-dependent vasodilation. Vascular rings of rabbit thoracic aorta were mounted for isometric tension recording in a flow chamber filled with physiological saline solution. The flow chamber contained a stir bar and was mounted on a magnetic stirrer to induce vortical flow. Norepinephrine (NE, 10(-6) M) induced contraction of the vascular rings. Bovine endothelial cells on microcarrier beads added to the chamber had little effect on contraction to NE in the absence of flow. Flow induced endothelium-dependent relaxation of the vascular rings that was dependent on the flow rate. Relaxations were annulled or reversed to a contraction with methylene blue, bovine hemoglobin, or N-monomethyl-L-arginine. Conversely, N-acetyl-L-cysteine augmented the flow-mediated relaxation. Furthermore, in the presence of N-acetyl-L-cysteine, the half-life of the endothelium-dependent relaxing factor was increased. In conclusion, the stimulus of flow induces the release by endothelial cells of a diffusible, short-lived factor with the attributes of a nitrovasodilator. The action of this endogenous vasodilator is augmented by the reduced thiol N-acetyl-L-cysteine.
Cooke
J P
JP
Division of Vascular Medicine and Atherosclerosis, Brigham and Women's Hospital, Boston 02115.
Stamler
J
J
Andon
N
N
Davies
P F
PF
McKinley
G
G
Loscalzo
J
J
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001775:Blood Circulation / Q000502:physiology*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009574:Nitro Compounds / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000378:metabolism*
D006454:Hemoglobins; D009574:Nitro Compounds; D014665:Vasodilator Agents; D008751:Methylene Blue; D000111:Acetylcysteine; D009638:Norepinephrine