Key result
High perfusion flow in rat mesenteric arterial beds increased perfusion pressure and stimulated the release of NO and ET-1, demonstrating that vascular tone is regulated by interacting endothelium-derived factors.
Flow-induced changes in vascular tone in the rat mesenteric arterial bed are subtly regulated by the interaction of endothelium-derived factors including NO, EDHF, and ET-1.
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Rat data implicate NO-ET-1 interplay in flow-mediated mesenteric tone; leaves open translation to human endothelial dysfunction.
We studied rat mesenteric arterial beds to determine the relationship between the effects of flow-induced shear stress and agonists on mesenteric vasoreactivity. When beds were perfused at gradually increasing flow rates, perfusion pressure was flow rate-dependently increased. The flow rate-mediated increase in perfusion pressure was significantly enhanced by N(G)-nitro-L-arginine (L-NOARG) plus methylene blue (MB) and slightly enhanced by treatment with tetraethylammonium (TEA). In the presence of L-NOARG, MB, TEA, and indomethacin, the flow rate-induced increase in perfusion pressure was significantly enhanced, but this enhancement was significantly inhibited by combined treatment with BQ-123 plus BQ-788 (ET(A)- and ET(B)- receptor antagonists, respectively). The ET-1 content of the perfusate was significantly increased following combined pretreatment with L-NOARG, MB, TEA, and indomethacin at a high flow rate. The methoxamine-induced contraction was significantly enhanced by NOS inhibition in both high- and low- flow-treated groups. The released nitrite level was significantly greater in high-flow-loaded than in the low-flow-loaded beds. We conclude that in this model, the response of vascular tone to flow stimulation is subtly regulated by endothelium-derived factors (especially, NO, endothelium-derived hyperpolarizing factor, and ET-1), and that these factors interact with each other.
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Matsumoto et al. (2004) studied Healthy (animal model). High perfusion flow rate vs. Low perfusion flow rate (5 ml/min) was evaluated on Perfusion pressure and release of endothelium-derived factors (ET-1, NO). High perfusion flow in rat mesenteric arterial beds increased perfusion pressure and stimulated the release of NO and ET-1, demonstrating that vascular tone is regulated by interacting endothelium-derived factors.
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