Role of nitric oxide and endothelium in the flow-induced dilation of rat coronary arteries under two preconstriction conditions

1. Pressure-induced tone and flow-induced dilations were studied in a rat p erfused epicardial coronary artery mounted in an arteriograph, Spontaneous tone was assessed in arteries submitted either to 60 or 90 mmHg intralumina l pressure either under control conditions, after incubation with N-G-nitro -L-arginine methyl ester (L-NAME; 100 mu mol/L) or after endothelial denuda tion. Flow-induced dilation was quantified under these conditions in prepar ations either submitted to 60 mmHg and preconstricted with 10 mu mol/L 5-hy droxytryptamine (5-HT) or exhibiting spontaneous tone at 90 mmHg. 2, Spontaneous tone was greater at 90 mmHg compared with tone obtained at 6 0 mmHg (21+/-2 vs 10+/-2 % reduction of the fully dilated diameter after so dium nitroprusside incubation, respectively). Incubation with L-NAME or rem oval of the endothelium significantly increased spontaneous tone at both pr essures compared with control. 3, In arteries submitted to 60 mmHg and preconstricted with 10 mu mol/L 5-H T, Bow (0-800 mu L/min) induced a continuous dilation (maximal value 63+/-4 %), As a function of how shear stress first increased and then plateaued at values of approximately 76+/-6 dyn/cm(2), After L-NAR IE incubation or end othelial denudation, the how-induced dilation was reduced to the same exten t and was obtained for higher values of shear stress (172+/-14 and 150+/-14 dyn/cm(2), respectively). 4. In arteries exhibiting spontaneous tone, starting flow led, first, to a constriction followed by a dilation up to 76+/-4 % of the initial tone. Inc ubation with L-NAME greatly altered flow-induced dilation. Endothelium remo val further reduced the dilation obtained for very high values of shear str ess (up to 300 dyn/cm(2)), 5. The present study shows that different patterns of vasodilation induced by how can be observed, depending on the initial vasoconstrictor stimulus. In 5-HT-preconstricted arteries, flow-induced dilation appears to he fully dependent on the synthesis and release of nitric oxide. In arteries with sp ontaneous tone, a vasoconstrictor substance could be released for low value s of how Nitric oxide is mainly, but not exclusively, responsible for the v asodilation, For both experimental conditions, removal of the endothelium g reatly reduced the response, but a dilation was still observed.