DOES ELEVATED NITRIC-OXIDE PRODUCTION ENHANCE THE RELEASE OF PROSTACYCLIN FROM SHEAR STRESSED AORTIC ENDOTHELIAL-CELLS

Nitric oxide (NO) enhances prostacyclin (PGI(2)) production in agonist -stimulated endothelial cells, while peroxynitrite formed from NO and superoxide action has been shown to activate cyclooxygenase, Using cul tured bovine aortic endothelial cells (BAEC) exposed to arterial level s of laminar shear stress of 25 dynes/cm(2), we tested the hypothesis that NO mediated the elevated synthesis of PGI(2) by shear stressed en dothelium, Shear stress caused a large and rapid burst and sustained r elease of NO and PGI(2) with the cumulative production at 1 hr enhance d 9,96-fold (n = 4, p < 0.005) and 9.16-fold (n = 3, p < 0.005), respe ctively, over stationary control production of 0.0257 nmol-NO/cm(2)-BA EC and 0.0193 ng-PGI(2)/cm(2)-BAEC. The NO synthase inhibitors, N-G-ni tro-L-arginine methyl ester (100 mu M, LNAME) and N-G-nitro-L-arginine (10 mu M, LNA), caused 87.5 and 65% reductions (n = 3, p < 0.02) of c umulative NO release at 1 hr, respectively, and 45 and 55% reductions (n = 3, p = 0.025) of PGI(2) release, respectively. About half of the elevated production of PGI(2) in shear stressed cells was due to NO-de pendent signaling, indicating that hemodynamic control of these two di latory molecules is partially coupled. (C) 1997 Academic Press.