Does elevated nitric oxide production enhance the release of prostacyclin from shear stressed aortic endothelial cells?
Nitric oxide (NO) enhances prostacyclin (PGI2) production in agonist-stimulated endothelial cells, while peroxynitrite formed from NO and superoxide anion has been shown to activate cyclooxygenase. Using cultured bovine aortic endothelial cells (BAEC) exposed to arterial levels of laminar shear stress of 25 dynes/ cm2, we tested the hypothesis that NO mediated the elevated synthesis of PGI2 by shear stressed endothelium. Shear stress caused a large and rapid burst and sustained release of NO and PGI2 with the cumulative production at 1 hr enhanced 9.96-fold (n = 4, p < 0.005) and 9.16-fold (n = 3, p < 0.005), respectively, over stationary control production of 0.0257 nmol-NO/cm2-BAEC and 0.0193 ng-PGI2/cm2-BAEC. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (100 microM, LNAME) and N(G)-nitro-L-arginine (10 microM, LNA), caused 87.5 and 65% reductions (n = 3, p < 0.02) of cumulative NO release at 1 hr, respectively, and 45 and 55% reductions (n = 3, p = 0.025) of PGI2 release, respectively. About half of the elevated production of PGI2 in shear stressed cells was due to NO-dependent signaling, indicating that hemodynamic control of these two dilatory molecules is partially coupled.
Wang
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Department of Chemical Engineering, State University of New York, Buffalo 14260, USA.
Diamond
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SL
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D013314:Stress, Mechanical
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester